Number Of Ia Research Articles

The Modification of Al-Si Casting Alloys: Important Practical and Theoretical Aspects

A review is given of the modification of aluminum-silicon casting alloys. The mechanisms involved and important practical aspects are described. While a number of IA and IIA elements and several lanthanides produce a modified eutectic, only strontium and sodium have found significant commercial application. They react with and remove aluminum phosphide (AlP), an effective nucleant for silicon, and produce a fine fibrous eutectic. The resulting as-cast structure has improved ductility. In heat treated castings it is possible to reduce the solution time when a modifier is employed. The result is a significant cost saving—usually ten or more times the cost of the modifier addition. Modification may change the relative formation of porosity and shrinkage in a casting. This subject has been the subject of a great deal of controversy and confusion in the past, but recent research in Australia has clarified the mechanisms involved. This work is summarized and practical guidelines are offered for the foundryman. The modifiers strontium and sodium are poisoned by phosphorus, antimony and bismuth. Consequently, the levels of these impurities should be monitored carefully in secondary alloys.

Immobilization stress suppresses cutaneous delayed‐type hypersensitivity reaction induced by gastrointestinal sensitization in mice: association with Langerhans cell of the forestomach

AbstractPsychological stress (PS) has various influences on allergic diseases. Although gastrointestinal sensitization induces hypersensitivity reactions in the skin, such as urticaria and dermatitis, due to food or drug allergy, the effect of PS on the gastrointestinal sensitization phase remains unclear. We administered 2,4,6‐trinitrochlorobenzene (TNCB) to BALB/c mice intragastrically (gastrointestinal sensitization). After 4 days, we elicited a cutaneous delayed‐type hypersensitivity (DTH) reaction by applying TNCB to the ear. We examined the effects of immobilization stress (IS) before gastrointestinal sensitization and elicitation on the cutaneous DTH (CDTH) by measurement of the thickness of the swollen ear, morphological changes and the number of Ia molecule‐positive Langerhans cells (Ia + LC) in the forestomach, and serum corticosterone (CORT) concentration. In addition, we studied the effect of pre‐administration of a glucocorticoid receptor antagonist (RU486). CDTH was suppressed significantly with application of IS for more than 6 h prior to gastrointestinal sensitization. Simultaneously, Ia + LC became smaller and round in shape and decreased in number. The serum CORT concentration doubled following IS for more than 2 h, and these changes were suppressed by pre‐administration of RU486. The results indicate that IS suppresses gastrointestinal sensitization, probably in association with suppression of the antigen‐presenting function of the Ia + LC by elevation of steroid hormones. Copyright © 2008 John Wiley & Sons, Ltd.

Evidence that ultraviolet B radiation transiently inhibits emigration of Langerhans cells from exposed epidermis, thwarting contact hypersensitivity induction.

Langerhans cells (LC) play a critical role in the induction of contact hypersensitivity (CH), and ultraviolet B radiation (UVR) impairs CH induction in UVB-susceptible (UVB-S) mice via a TNF-alpha-dependent mechanism. A possible explanation of this effect is that UVR impairs CH in UVB-S mice by immobilizing LC transiently in the epidermis and upper dermis, thereby preventing their timely migration to draining lymph nodes. To test this hypothesis we examined in vitro and in vivo the effects of in vivo UVR on migration of Ia(+) cells from skin of UVB-S and UVB-resistant (UVB-R) mice. Dorsal surfaces of ears of mice were irradiated with 400 J/cm(2) UVB and either explanted in vitro or transplanted orthotopically to the thoracic wall of syngeneic recipients. After 24, 48, and 72 h the epidermis was recovered from these explants/grafts and the number of Ia(+) cells determined by immunohistochemistry. Culture medium obtained after explants were removed was also evaluated for content of Ia(+) cells. The density of Ia(+)-bearing cells in the epidermis of cultured untreated skin explants and of grafted skin fell progressively for both UVB-S and UVB-R skin during the observation period. The rate of decline in Ia(+) cells density during this interval was greatly impaired if the skin was exposed to UVR prior to excision; this effect was seen equally in UVB-S and UVB-R skin. Recovery of Ia(+) cells in the medium after removal of cultured untreated skin explants was maximum after 24 h and comparable in UVB-S and UVB-R skin. However, the number of Ia(+) cells recovered in the medium from UVB-exposed skin was significantly reduced only if the skin donor was UVB-S. We conclude that the ability of UVR to impede LC migration from epidermis is significantly greater for UVB-S mice, accounting in part for the failure of these mice after UVR to acquire CH.

Development of apoptosis and changes in lymphocyte subsetsin thymus, mesenteric lymph nodes and Peyer's patches of mice orally inoculated with T-2 toxin

Development of apoptosis and changes in lymphocyte subsets were examined mainly by flow cytometer in thymus, mesenteric lymph nodes and Peyer's patches of mice up to 24 hours after oral inoculation with T-2 toxin (10 mg/kg). T-2 toxin attacked Peyer's patches first, then mesenteric lymph nodes, and finally thymus in relation to the course of enteric absorption of orally inoculated T-2 toxin. The degree of lymphocyte apoptosis was prominent in the thymus, moderate in the Peyer's patches, and somewhat mild in the mesenteric lymph nodes, suggesting the difference in lymphocyte population susceptible to T-2 toxin. As to the changes in lymphocyte subsets, CD4+ CD8+ T cells were most sensitive to T-2 toxin, and CD4+ CD8- T cells were more severely depressed than CD4- CD8+ T cells in the thymus. In the mesenteric lymph nodes, CD3+ cells was more clearly affected than CD19+ cells, and the numbers of CD4+ and CD8+ cells were similarly decreased. In the Peyer's patches, the numbers of CD3+, CD 19+, CD4+ and CD8+ cells were unexceptionally decreased. In addition, among IgM+, IgG+ and IgA+ B cells, the number of IA+ B cells which are more important in the mucosal immunity was most severely affected.

Glucocorticoid-induced apoptosis of dendritic cells in the rat tracheal mucosa.

Dendritic cells are antigen-presenting cells that constitutively express high levels of major histocompatibility complex class II (Ia) antigen on their plasma membrane. Previous studies have shown that the number of dendritic cells in the rat airway mucosa decreases rapidly after glucocorticoid treatment. We sought to determine whether apoptosis contributes to this steroid-induced cell decrease. Dendritic cells in tracheal whole mounts were revealed by immunoperoxidase staining using the OX-6 (anti-Ia) monoclonal antibody. In untreated rats, a dense network of Ia-immunoreactive (Ia+) cells with highly branched cytoplasmic processes was observed just beneath the tracheal epithelium (1,405 +/- 140 cells/mm2 mucosa; mean +/- SEM, n = 6). In rats treated with dexamethasone (10 mg/kg, intraperitoneally), four distinct changes in dendritic cell morphology were evident 4 to 8 h after injection: (1) appearance of large Ia+ granules in cytoplasmic processes, (2) narrowing of cytoplasmic processes, (3) loss of Ia immunoreactivity from the cell surface, and (4) fragmentation of cells into small Ia+ bodies. These changes accompanied a 56% decrease in the number of Ia+ cells over 8 h. The contribution of apoptosis to this decrease in Ia+ cells was determined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) of nucleosomal DNA fragments in histologic sections. The number of TUNEL+ bodies increased from a control value of 174 +/- 47 bodies/mm2 mucosa to 2,108 +/- 294 bodies/mm2 mucosa at 4 h and 936 +/- 343 bodies/ mm2 mucosa at 8 h (n = 4 rats per time point). The location of TUNEL+ bodies closely corresponded to that of Ia+ cells stained in adjacent histologic sections. We conclude that apoptosis contributes to the rapid decrease in airway dendritic cells after glucocorticoid treatment.

In vivo inhibition of cell-mediated and humoral immune responses to cellular antigens by SV-IV, a major protein secreted from the rat seminal vesicle epithelium

Microgram amounts of protein SV-IV, a major secretory protein produced by adult rat seminal vesicle epithelium, markedly decrease the mouse humoral immune response to cellular xenogeneic or allogeneic antigens (sheep red blood cells (SRBC) or mouse epididymal spermatozoa). The significant reduction in the total number of splenocytes and their main cell subsets in SRBC-immunized mice, the dramatic decrease in the number of Ia + splenic T cells and the marked inhibition of splenocyte ability to respond in vitro to polyclonal mitogen stimuli suggest that the macrophage accessory cells are the primary target of the SV-IV immunosuppressive activity in vivo. Moreover, the infection of SV-IV-treated mice with Salmonella typhimurium produced an increased mortality of the experimental animals associated with a marked decrease of the phagocytic and intracellular killing activities of their peritoneal macrophages.

Mechanism for macrophage activation against Corynebacterium parvum--participation of T cells and its lymphokines.

It is well known that Corynebacterium parvum activates macrophages to produce tumor necrosis factor (TNF). It is suspected that the activation of macrophages by C. parvum requires T-cell participation. The purpose of this study was to confirm that T cells participate in the activation of macrophages by C. parvum. TNF production in vitro from the spleen cells of BALB/c(-)+/+ mice was abrogated completely by the pre-treatment of spleen cells with anti-Ia antiserum and complement, indicating that Ia+ cells are the source of TNF. TNF production was not elicited at all in BALB/c-nu/nu mice. However, there was an increase in the number of Ia+ cells as well as an increase in the weight of spleen and liver. Supernatant from a culture of spleen cells stimulated with phytohemagglutinin-P (a PHA-induced lymphokine) made it possible for BALB/c-nu/nu mice to produce TNF, associated with an induction of Lyt-1+ cells and Lyt-2+ cells. However, treatment with the lymphokine did not augment the increases of Ia+ cells or liver and spleen weights. These results suggest that increasing the number of Ia+ cells is not sufficient to bring about TNF production; Ia+ cells must also be stimulated by T cells or T-cell lymphokines in order to produce TNF. These results suggest that T cells play an essential role in the activation of Ia+ cells against C. parvum.

Interleukin-10 enhances HIV-1 expression in a chronically infected promonocytic cell line (U1) by a TNFα-independent mechanism

Chronic relapsing experimental autoimmune encephalomyelitis (CR-EAE) was induced in Lewis rats by inoculation with guinea pig spinal cord and adjuvants and treatment with low dose cyclosporin A (CsA). Acute EAE was induced by the same method without CsA treatment. Immunocytochemistry and flow cytometry were used to assess inflammatory cells and MHC class II (Ia) antigen expression in the central nervous system of these rats. The inflammatory infiltrate was composed mainly of CD4+ T cells and macrophages, and αß T cells constituted about 65% of the CD2+ T cells. After recovery from acute EAE and during the first remission of CR-EAE, the number of T cells was significantly less than in the preceding episodes. The number of T cells was higher in the second episode of CR-EAE than in the first remission. Throughout the course of CR-EAE, the majority of the CD2+ T cells were CD45RC−. The ratio of IL-2R+ cells to CD2+ cells ranged from 10.5 to 24.0%. The ratio of CD4+ T cells to B cells was lower in the later episodes of CR-EAE than in the first episode. Ia antigen was expressed on filtrating round cells at all stages of CR-EAE and on microglial cells (identified by dendritic morphology) with increasing intensity throughout the course of CR-EAE. With flow cytometry, the number of Ia+ cells obtained from the spinal cord rose throughout the course of CR-EAE. The number of FSClowOX1low cells, which we consider represent microglia, also increased during the course of CR-EAE.

Okadaic acid regulates IL-6 and IL-6 receptor expression of human myeloma cells

Chronic relapsing experimental autoimmune encephalomyelitis (CR-EAE) was induced in Lewis rats by inoculation with guinea pig spinal cord and adjuvants and treatment with low dose cyclosporin A (CsA). Acute EAE was induced by the same method without CsA treatment. Immunocytochemistry and flow cytometry were used to assess inflammatory cells and MHC class II (Ia) antigen expression in the central nervous system of these rats. The inflammatory infiltrate was composed mainly of CD4+ T cells and macrophages, and αß T cells constituted about 65% of the CD2+ T cells. After recovery from acute EAE and during the first remission of CR-EAE, the number of T cells was significantly less than in the preceding episodes. The number of T cells was higher in the second episode of CR-EAE than in the first remission. Throughout the course of CR-EAE, the majority of the CD2+ T cells were CD45RC−. The ratio of IL-2R+ cells to CD2+ cells ranged from 10.5 to 24.0%. The ratio of CD4+ T cells to B cells was lower in the later episodes of CR-EAE than in the first episode. Ia antigen was expressed on filtrating round cells at all stages of CR-EAE and on microglial cells (identified by dendritic morphology) with increasing intensity throughout the course of CR-EAE. With flow cytometry, the number of Ia+ cells obtained from the spinal cord rose throughout the course of CR-EAE. The number of FSClowOX1low cells, which we consider represent microglia, also increased during the course of CR-EAE.

Inflammatory cells, microglia and MHC class II antigen-positive cells in the spinal cord of Lewis rats with acute and chronic relapsing experimental autoimmune encephalomyelitis

Chronic relapsing experimental autoimmune encephalomyelitis (CR-EAE) was induced in Lewis rats by inoculation with guinea pig spinal cord and adjuvants and treatment with low dose cyclosporin A (CsA). Acute EAE was induced by the same method without CsA treatment. Immunocytochemistry and flow cytometry were used to assess inflammatory cells and MHC class II (Ia) antigen expression in the central nervous system of these rats. The inflammatory infiltrate was composed mainly of CD4 + T cells and macrophages, and αß T cells constituted about 65% of the CD2 + T cells. After recovery from acute EAE and during the first remission of CR-EAE, the number of T cells was significantly less than in the preceding episodes. The number of T cells was higher in the second episode of CR-EAE than in the first remission. Throughout the course of CR-EAE, the majority of the CD2 + T cells were CD45RC −. The ratio of IL-2R + cells to CD2 + cells ranged from 10.5 to 24.0%. The ratio of CD4 + T cells to B cells was lower in the later episodes of CR-EAE than in the first episode. Ia antigen was expressed on filtrating round cells at all stages of CR-EAE and on microglial cells (identified by dendritic morphology) with increasing intensity throughout the course of CR-EAE. With flow cytometry, the number of Ia + cells obtained from the spinal cord rose throughout the course of CR-EAE. The number of FSC lowOX1 low cells, which we consider represent microglia, also increased during the course of CR-EAE.

Involvement of t cell immunity in the transient thyroid inflammation induced by iodide in goitrous balb/c and nude mice

To evaluate the involvement of T cell immunity in the thyroiditis induced in goitrous mice by iodide administration, we analyzed the immunological changes happening in the thyroid glands and lymph nodes during goiter involution in balb/c and athymic nude mice of similar background. In both balb/c and nude mice, goiter involution was characterized by thyroid cell necrosis and inflammation. In balb/c mice, the inflammatory infiltrate was made of numerous Ia+ cells. Their number was unchanged during goiter development, but was significantly increased after 2 days of involution and remained high after 8 days. CD4+ and CD8+ T cells were also observed, some of which were clearly activated since they expressed the receptor for Interleukin-2 (IL-2R). The numbers of CD4+, CD8+ and IL-2R+ T cells were increased during goiter as compared to control mice, and they reached a maximum at day 1 of involution. In nude mice, unexpectedly, CD4+ and CD8+ T cells were also found in the thyroid. Their numbers, as well as the number of Ia+ cells, were significantly increased at the onset of involution, but they remained systematically lower than in the corresponding groups of balb/c mice. Iodide treatment of goitrous mice also induced modifications of the lymph nodes draining the thyroid: enlargement of the paracortical T zone, presence of germinal centers in cortical follicles, and increase of the density of IL-2R+ cells. Mesenteric lymph nodes taken as controls were unchanged. Thus, three observations suggest the involvement of T cell immunity in iodine-induced thyroid inflammation: 1. Infiltration of Ia+, CD4+, CD8+ and IL-2R+ cells. 2. Signs of stimulation in thyroid lymph nodes, 3. Significant differences between balb/c and nude mice, in which the inflammatory reaction is weaker.

Enhancement of Ia antigen expression and nonproliferating cells correlates with metastatic capacity.

Maintaining B16F10 tumor cells in stirring culture for 48 h leads to an increase in lung and liver colonizing capacity in comparison with cells in adherent culture. Parallel to the increased metastatic capacity, we have observed a decrease in the proliferative rate of tumor cells (as the percentage of proliferating cell nuclear antigen-positive cells) and an increase in the population of tumor cells expressing Ia antigen. These results are not exclusive to B16F10 cells, since the same results were obtained when we analyzed 3LL cells maintained in identical culture conditions. In all the tumor lines tested, we found an association between the nonproliferating and the Ia-positive cell populations. We induced Ia expression by treating B16F10 cells in adherent culture with the lectin concanavalin A and again, coincident with an increase in metastatic capacity, we found the same association between the two parameters analyzed--nonproliferating state and Ia antigen expression. In addition, it was found that B16F10 cells induce lymphocytic proliferation, and a direct relationship was established between the number of Ia+ cells and lymphocytic proliferation.

Roles of CD4+ and CD8+ cells in UVB-induced suppression of splenic alloantigen-presenting function.

Whole body ultraviolet light (UV) radiation causes systemic immunosuppression. Splenic antigen-presenting cell (APC) activity is decreased by UV radiation. To determine whether splenic CD4+ or CD8+ cells are involved in the UV-induced depression of splenic alloantigen-presenting function, we investigated the effect of in vivo UV radiation on the splenic stimulatory function in allogeneic mixed lymphocyte reaction in mice after the elimination of CD4+ or CD8+ cells by administering anti-CD8 or anti-CD4 Ab. Ab-treated and non-treated mice were exposed to UVB radiation (2.5 kJ/m2) twice or eight times. Two exposures to UVB radiation significantly suppressed the splenic alloantigen-presenting function of mice previously treated with anti-CD4 Ab, but hardly affected that of anti-CD8 Ab-treated or non-treated mice 2 days after the last radiation. On the other hand, eight exposures to UVB radiation suppressed this function in all mice. FACS analysis revealed that the UV-induced suppression is not associated with a significant decrease in the number of IA+ cell, as stimulator cells. It is suggested that CD4+ cells are somewhat preventive of the UV-induced depression of splenic allo-antigen-presenting function.

Ontogenic development of macrophage subpopulations and Ia-positive dendritic cells in fetal and neonatal rat spleen.

Development, differentiation, and distribution of macrophage subpopulations and Ia+ dendritic cells in the fetal and neonatal rat spleen were investigated by means of double immunohistochemical staining and immunoelectron microscopy. To characterize these cell populations, a panel of anti-rat macrophage monoclonal antibodies (RM-1, ED2, ED3, TRPM-3, Ki-M2R) and an anti-rat Ia antibody (OX6) were used. In the fetal rat spleen, macrophages were first detected by RM-1 at fetal day 15. ED2+ and/or Ki-M2R+ macrophages appeared at fetal day 16. TRPM-3+ and/or ED3+ macrophages appeared a day later. During the fetal and neonatal development, ED2+ and TRPM-3+ macrophages differentiated independently, maturing into red pulp macrophages and marginal metallophilic and marginal zone macrophages respectively. Intimate topographical relations were observed between ED2+ macrophages and hematopoietic cells and between TRPM-3+ macrophages and marginal zone lymphocytes. Ia+ cells were first observed around arterioles at fetal day 15. In the fetal and neonatal period, the number of Ia+ cells gradually increased, their shape became dendritic, and they matured into interdigitating cells in the inner periarteriolar lymphatic sheath. In ontogeny, Ia+ dendritic cells were not stained with ED2 or TRPM-3. These results suggest that ED2+ macrophages, TRPM-3+ macrophages, and Ia+ dendritic cells are distinct cell lines that pursue independent developmental process in spleen ontogeny.

Antigen-presenting activity of draining lymph node cells from mice painted with a contact allergen during ultraviolet carcinogenesis.

The induction of skin cancers in mice by chronic UV irradiation is accompanied by a decrease in the numbers of Ia+ and Thy-1+ dendritic cells in the epidermis early in the course of UV irradiation. Subsequently, the number of Ia+ cells, but not Thy-1+ cells, increases until the time of tumor development. To assess the functional significance of these changes in cutaneous immune cells, and to help define the role these cells may play in immune surveillance against skin cancers, we tested the afferent immunologic capability of the skin during the development of UV-B radiation-induced skin cancers. Afferent immune function was measured by testing the Ag-presenting capacity of draining lymph node (DLN) cells from mice sensitized epicutaneously with dinitrofluorobenzene. A reduced contact hypersensitivity response was induced in mice immunized with DLN cells from UV-irradiated mice that had been sensitized with hapten on UV-irradiated skin. This decreased reactivity was present during the entire latent period of tumor development. However, in tumor-bearing mice, the DLN cells from UV-irradiated, sensitized animals exhibited normal Ag-presenting activity. DLN cells from UV-irradiated mice sensitized on ventral, unirradiated skin exhibited normal Ag-presenting activity. The lowest amount of Ag-presenting activity in the draining lymph nodes of UV-irradiated mice correlated temporally with the lowest number of Ia+, adenosine triphosphatase+ dendritic epidermal cells in the UV-irradiated skin. At least during the early part of the tumor latent period, an increase in the number of these cells was paralleled by an increase in the Ag-presenting activity of the DLN cells. In contrast, the number of Thy-1+ dendritic epidermal cells in UV-irradiated skin did not correlate with the Ag-presenting activity. Thus, the decrease in the number of identifiable epidermal Langerhans cells early in the course of chronic UV irradiation correlated with a decrease in Ag-presenting activity after sensitization through the UV-irradiated skin. These studies demonstrate that the afferent arm of the cutaneous immune response is impaired in the site of tumor development throughout the latent period of UV carcinogenesis.

Antigen-Presenting Cells in Essential Fatty Acid—Deficient Murine Epidermis: Keratinocytes Bearing Class II (Ia) Antigens May Potentiate the Accessory Cell Function of Langerhans Cells

Essential fatty acid deficiency (EFAD) is a useful model for studying the role of (n-6) fatty acid metabolism in normal physiology. Because cutaneous manifestations are among the earliest signs of EFAD and because abnormalities in the distribution and function of tissue macrophages have been documented in EFAD rodents, we studied the distribution and function of Class II MHC (Ia) antigen-bearing cells in EFAD C57B1/6 mouse epidermis. Immunofluorescence studies revealed 1.9-9.6 (mean +/- SEM = 5.2 +/- 2.6) times more class II MHC (Ia) antigen-bearing epidermal cells in suspensions prepared from EFAD as compared to normal skin. Analysis of epidermal sheets demonstrated similar numbers of dendritic Ia+ and NLDC145+ cells in EFAD and normal epidermis, however. This discrepancy occurred because some keratinocytes in EFAD epidermal sheets expressed class II MHC (Ia) antigens, whereas keratinocytes in normal mouse epidermis did not. Two-color flow cytometry confirmed that all Ia+ cells in normal epidermis are Langerhans (Ia+ NLDC145+) cells, whereas Ia+ cells in EFAD epidermis are comprised of Langerhans cells and a subpopulation of keratinocytes (Ia+ NLDC145-). Similar levels of Ia antigens were expressed on EFAD and normal Langerhans cells. EFAD and normal epidermal cells were also compared in several in vitro assays of accessory cell function. Epidermal cells prepared from EFAD C57B1/6 mice present the protein antigen DNP-Ova to primed helper T cells more effectively than epidermal cells prepared from normal animals. EFAD epidermal cells are also more potent stimulators of T cells in primary and secondary allogeneic mixed lymphocyte-epidermal cell reactions than normal epidermal cells. The functional differences between EFAD and normal epidermal cells do not appear to result from increased cytokine release or decreased prostaglandin production by EFAD epidermal cells. In view of these findings and the observation that the antigen-presenting cell activity of EFAD epidermal cells correlates with the number of Ia+ keratinocytes in epidermal cell preparations, Ia+ keratinocytes (in the presence of Langerhans cells) may potentiate cutaneous immune responses in vitro and perhaps in vivo as well. These results also suggest that (n-6) fatty acids or metabolites of (n-6) fatty acids are involved in regulating the expression of class II MHC (Ia) antigens by keratinocytes in vivo.

Interleukin-1 decreases the number of Ia+ epidermal dendritic cells but increases their expression of Ia antigen.

It is generally accepted that ETAF/IL-1 is produced in epidermis by both keratinocytes and Langerhans' cells. We have studied the density and morphology of Ia+ epidermal dendritic cells in mice after systemic or intracutaneous injection of recombinant IL-1 beta. We found that rIL-1 beta decreased the density of Ia+ dendritic cells in the time period 2-7 days after rIL-1 beta administration. However, the remaining dendritic cells were enlarged and more arborized with increased expression of Ia antigen 1-4 days after injection of rIL-1 beta. The implication of the results is that ETAF/IL-1 modulates the function of Langerhans' cells through autocrine and paracrine regulation.

Foreign body reaction against cellophane in the athymic nude mice.

There are no differences in the multinucleate cell formation in normal and athymic mice after the subcutaneous implantation of a cellophane strip. The number of Ia+ epitheloid cells and multinucleate foreign body giant cells was lower and the number of epitheloid cells sharing the marker of activated macrophages (M 57) was higher in athymic compared to normal mice. The epitheloid cells of athymic and euthymic animals exhibited no difference in the expression of Mac-2 molecule. The difference of the expression of surface markers between athymic and euthymic animals does not influence the foreign body giant cell formation.

5 The immune function of the endometrium

The endometrial mucosa is unique amongst mucosal sites in that it must mount an immune response against micro-organisms and resist tumour growth whilst tolerating sperm and the allogeneic fetus. Bacterial and viral infection in the uterus leads to local endometrial mucosal immune responses evidenced by the secretion of secretory component (SC), secretory IgA (sIgA) and IgG. The secretion of these molecules is under hormonal control. Trafficking of locally sensitized lymphocytes to other mucosae does not appear to occur, whereas priming at other mucosal surfaces leads to memory responses to antigen in the uterus. Proclivity to local immune function is related to sparse lymphatic supply to the endometrium together with a local distribution of antigen-presenting dendritic cells. During pregnancy, particularly in the region of the decidua and embryo, the number of Ia+ cells and the lymphatic supply become diminished. The antigenic status of sperm may lead to certain types of maternal sensitization. However, immunosuppressive factors in seminal plasma protect the sperm on its passage up the female genital tract and diminish subsequent immunogenicity. On fertilization of the oocyte, an allogenic fetus develops, that potentially could stimulate production of maternal immune effectors. Endometrial cells of various types (macrophage, decidual, NK, T cells) interact via soluble factors leading to a local immunoprotection of the fetus. Similar factors appear to operate in resisting tumour growth in the uterus.

Tumor-induced alteration in macrophage accessory cell activity on autoreactive T cells.

Using a tumor-model system, differences in the accessory cell capabilities on autoreactive T cells of splenic macrophages from normal and tumor-bearing hosts (TBH) were assessed in the syngeneic mixed lymphocyte reaction. Tumor development caused a drop in autoreactivity. At 0 and 7 days of tumor growth, no drop in reactivity occurred when TBH macrophages were used as accessory cells and L3T4+ autoreactive T cells from normal mice were used as responder cells. However, by day 14, there was a 32% drop in reactivity, and by day 21 only 22% of the T cell reactivity remained when TBH macrophages were used as accessory cells. Alterations in macrophage Ia antigen during tumor growth were first investigated as the potential cause of reduced autoreactivity. Before tumor growth (day 0) 59% of the splenic macrophages were found to be Ia+. Day-7 TBH macrophages showed no difference in Ia antigen expression when compared to day 0 macrophages. However, by day 14, TBH macrophages showed a 9% decrease, and by day 21 they showed a 36% decrease in the number which were Ia+. Concomitant with the decrease in the number of Ia+ cells was a decrease in the density of Ia antigen expression on day-14 and -21 TBH macrophages. In day-14 and -21 TBH macrophages, two populations were seen that were Ia+. The first had a 10%-20% decrease in Ia antigen expression per cell while the second population had a greater than 50% drop in Ia antigen expression per cell. By titrating and mixing TBH macrophages with normal host macrophages, we assessed whether they could actively mediate suppression of autoreactive T cells. A titratable suppressive phenomenon was demonstrated using day-21 TBH macrophages. In contrast, day-7 and -14 TBH macrophages titrated with normal host macrophages had no effect on the syngeneic mixed lymphocyte reactivity. Lastly, we investigated whether the macrophage-mediated suppression was caused by increased prostaglandin secretion. Addition of indomethacin to cultures increased autoreactive T cell reactivity stimulated by normal or TBH macrophages (59% and 99% increase, respectively). Although indomethacin reduced suppression mediated by TBH macrophages, autoreactivity did not return to levels induced by untreated or indomethacin-treated cells from a normal host. Taken together, the data suggested that tumor growth modulates the function of macrophage accessory cells with autoreactive T cells in at least two ways: by decreasing Ia antigen expression and by increasing suppressor activity.