Ia Antigens Research Articles

The Medawar Prize Acceptance Speech 2022.

The Medawar Prize Acceptance Speech 2022.

Ia Antigen Expression by Human Malignant Lymphomas: Correlation With Conventional Lymphoid Markers

The Ia (p23,30) antigens are useful in determining the B- or T-cell origin of normal peripheral blood lymphocytes. However, exceptions to the preferential B-cell expression of Ia antigens exist, i.e., many plasma cells are Ia– and T cells are rarely Ia+. Therefore, we investigated Ia expression (assayed by direct immunofluorescence using heteroantisera) by cells isolated from 33 malignant lymphomas and 7 benign lymph nodes. This was compared with surface immunoglobulin (SIg) and sheep erythrocyte (SRBC) receptor (E rosette) expression. Results with normal lymph nodes were similar to those described for peripheral blood. Most lymph node B cells were Ia+SIg+. Occasional Ia+SIg– B cells and rare Ia+ T cells were present. Ia antigens were expressed in parallel with SIg in 15 of 19 B-cell lymphomas. In 4 B-cell lymphomas, substantial numbers of neoplastic Ia+SIg– cells were also present, suggesting the presence of neoplastic cells at varying stages of differentiation. Heterogeneity was also seen in those lymphomas associated with monoclonal proteins, as small numbers of Ia+ and Ia– plasma cells were present. Seven cases expressed the T-cell (la–SIg–E+) phenotype. The common acute lymphoblastic leukemia phenotype (Ia+SIg–E–) was rarely expressed and may be uncommon among lymphomas. Three lymphomas expressing the Ia+E+ phenotype were shown to be B-cell malignancies whose SIg had SRBC specificity. One Ia 4 T-cell lymphoproliferative disorder was found. Thus, Ia antigens are useful B-cell markers in most instances. Furthermore, their enumeration allows the demonstration of phenotype heterogeneity in B-cell malignancies, analogous to that described for T-cell malignancies.

Retinoic acid synthesis by a population of choroidal stromal cells

Choroidal all- trans -retinoic acid (atRA) may play a key role in the control of postnatal eye growth in a variety of vertebrates through modulation of scleral extracellular matrix synthesis and may therefore play a crucial role in the development of myopia. In the chick eye, choroidal atRA synthesis is exclusively regulated by its synthesizing enzyme, retinaldehyde dehydrogenase 2 (RALDH2). In chicks and humans, RALDH2 has been detected in a population of hitherto uncharacterized choroidal cells.Therefore, the aim of this study was to identify the RALDH2+ cell type(s) in the choroid and determine how these cells modulate atRA concentrations during periods of visually guided eye growth. Chicks wore translucent goggles on one eye for 10 days and choroids were analyzed for RALDH activity and RALDH2 protein expression at days 0, 1, 4, 7, 15 following removal of the goggle (“recovery”); choroids from contralateral eyes served as controls. The presence of RALDH2+ cells was assessed in chick choroid wholemounts using multiphoton microscopy. RALDH2 protein expression was measured by western blot and RALDH2 activity was assessed via HPLC quantification of atRA. Cell proliferation was assessed by BrdU-labelling in combination with RALDH2-immunohistochemistry. For characterization of RALDH2+ cells, immunohistochemistry for various tissue specific markers was applied in chicken (Ia antigen, CD5, Col1-propeptide, desmin, IgY, L-Cam, Cadherin1, MHC-II; Tcr-γδ, vimentin) and human donor tissue (α-smooth-muscle-actin, CD’s 31/34/68/146, desmin, IBA1, LYVE-1, PGP9.5, vimentin) followed by confocal microscopy. In the chick and human choroid, RALDH2+ cells with variable morphology were present in the stroma and adjacent to choroidal blood vessels. In chick wholemounts, RALDH2+ cells were concentrated toward the choriocapillaris, and their number increased nearly linearly between 1 and 7 days of recovery and plateaued between 7 and 15 days compared to corresponding controls. A significant increase in choroidal RALDH2 protein concentration and atRA synthetic activity was observed by four days of recovery (↑107% and ↑120%) by western blot and HPLC, respectively. A 3-fold increase in RALDH2+/BrDU+ cells was observed following 4 days of recovery compared to controls (12.43 ± 0.73% of all RALDH2+ cells in recovering eyes as compared with 4.46 ± 0.63% in control eyes, p < 0.001). In chick choroids, the vast majority of RALDH2+ cells co-expressed Col1-propetide, but did not co-label with any other antibodies tested. In human choroid, some, but not all RALDH2+ cells colocalized with vimentin, but were negative for all other antibodies tested. RALDH2+ cells represent a novel cell type in the chick and human choroid. Our findings that some human RALDH2+ cells were positive for vimentin and all chick RALDH2+ cells were positive for Col1, suggest that RALDH2+ cells most closely resemble perivascular and stromal fibroblasts. The increased number of RALDH2+/BRDU+ cells following 4 days of recovery suggests that choroidal atRA concentrations are partially controlled by proliferation of RALDH2+ cells. The identification of this choroidal cell type will provide a broader understanding of the cellular events responsible for the regulation of postnatal ocular growth, and may provide new avenues for specifically targeted strategies for the treatment of myopia.

Abstract 336: Human Bone Contains Primitive Cells With Angiogenic and Immunomodulatory Properties

Previously, we have shown that treatments of cortical bone derived stem cells (CBSCs) reduce ventricular remodeling and improve cardiac functions in both mouse and pig myocardial infarction (MI) models. The goals of the present study were to isolate and characterize human CBSCs (hCBSCs). Using bone fragments obtained at the time surgeries, we isolated three morphologically distinctive hCBSC phenotypes; 1) sphere forming (SF); 2) epithelial like monolayer (ELM); and 3) larger and spindle shaped (LSS) phenotype. The hCBSC phenotypes grew without senescence in culture. Mean doubling time (hour) for SF, ELM, and LSS at the passage number 20 (P20) were 19.54, 21.21, and 20.3 respectively and at the P40 were 18.01, 17.13, and 20.56 respectively. All of the phenotypes were found to have surface expression of CD44; however, other markers detected (CD105, CD90, CD73, CD106, CD271, and CD133) on mouse CBSCs (mCBSCs) were not detected along with the markers not detected on the surface of mCBSCs (CD45, CD11b, CD31, CD34, CD117, and CD325). Erythrocytes (CD235a) and immune cell markers (CD2, CD3, CD14, CD16, CD19, and CD56) were also not detected. The hCBSCs were found without histocompatibility antigen Ia (MHC-Ia: HLA-A, HLA-B, and HLA-C) and MHC-II (HLA-DR); instead, they expressed soluble forms of MHC-Ib (HLA-G5, HLA-G6, and HLA-G7), potent inhibitor of natural killer cells and other immune cells. These features are commonly found in immune privileged cells. Further, the hCBSCs produced the immunomodulatory and anti-inflammatory factors (IL-4, IL-1RA, TGF-b and IL-10). Additionally, the hCBSCs secreted angiogenic factors that organize endothelial cells into tube like structures. From these results, the hCBSCs we isolated have totally different surface marker characteristics compared to any other known cells including mCBSCs. In addition to their angiogenic effects, the hCBSCs have immunomodulatory properties that could make them suitable for cell therapy targeting inflammatory diseases such post myocardial infarction remodeling.

Paternal antigen-specific proliferating regulatory T cells are increased in uterine-draining lymph nodes just before implantation and in pregnant uterus just after implantation by seminal plasma-priming in allogeneic mouse pregnancy

Paternal antigen-specific regulatory T (PA-specific Treg) cells play an important role in feto-maternal tolerance. To detect the PA-specific Tregs, female BALB/c mice were mated with male DBA/2 mice. Mls Ia antigen on DBA/2 mice is recognized by the T-cell receptor Vβ6; thus, CD4+Foxp3+Vβ6+ cells are recognized as PA-specific Treg cells. CD4+CD25+Vβ6+ cells effectively suppressed the allo-reactive proliferation of lymphocytes compared with that of CD4+CD25+Vβ6− cells. Vβ6+ PA-specific Treg cells expressed CCR4 and CCR5 on their surface. The frequency of Ki67+ PA-specific Treg cells among Treg cells was significantly increased in draining lymph nodes on day 3.5 post-coitus (pc; 6.8±1.1%, p<0.05) and day 5.5 pc (7.2±1.1%, p<0.05) in allogeneic pregnant mice compared with that in nonpregnant mice (2.7±0.2%). The frequency of Ki67+ PA-specific Treg cells in the uterus increased significantly after day 5.5 pc in allogeneic pregnant mice compared with that in nonpregnant mice (8.8±2.8% vs. 1.2±1.3%, p<0.05). However, Ki67-PA-specific Tregs did not change during pregnancy. To analyze the role of seminal fluid or sperm in Treg expansion, female BALB/c mice were mated with vasectomized DBA/2 male mice (VAS) or seminal vesicle-excised DBA/2 male mice (SVX). The frequency of Ki67+ PA-specific Treg cells did not increase in draining lymph nodes or uterus in BALB/c×DBA/2 (SVX) allogeneic mating mice. These findings suggest that the priming by seminal fluid is important for the induction of proliferating PA-specific Tregs in uterine-draining lymph nodes just before implantation and pregnant uterus after implantation, resulting in successful implantation and the maintenance of allogeneic pregnancy.

HLA Analysis of CD15+ Granulocytes of Leukemic Patients and Assessment of its Implication in Leukemia Immunotherapy

It is of common knowledge that most leukemic patients succumb to infectious complications beside dysfunction in proliferation/differentiation of hematopoietic cells . Recently, it has been shown by several groups that there is a locus specific HLA class I downregulation in the leukemic cells. However, the HLA status of the phenotypically/morphologically normal granulocytes which can cope up with the infectious complications are not known. Therefore it may be worthwhile to study the HLA status in these cell types. We, therefore, investigated the status of HLA-ABC and HLA-DR in the CD15 + granulocytes and observed a higher expression of HLA-DR in several leukemic samples in comparison to normal volunteers (NV). Our data also suggest that only CD15 + granulocytes of myeloid leukemia, a clonal stem cell disorder, have a tendency of decreased HLA class Ia antigen expression. Moreover CD15 + granulocytes of NV showed an enhanced HLA-DR expression in presence of leukemic cells. Interestingly, CD15 + granulocytes collected from normal volunteers were observed to have phagocytic oxidative burst activity towards HLA class Ia downregulated primary leukemic cells. We therefore suggest that neutrophil transplantation may be used for the treatment of leukemia.

Early Gestational Fetal NK Cells are Capable of Rejecting Prenatal Allografts Prior to the Expression of Receptors for MHC Class Ia Antigens

Early Gestational Fetal NK Cells are Capable of Rejecting Prenatal Allografts Prior to the Expression of Receptors for MHC Class Ia Antigens

Human Leukocyte antigen-G (HLA-G) and gastrointestinal malignancy.

Human Leukocyte antigen-G (HLA-G) and gastrointestinal malignancy.

Quantified Colocalization Reveals Heterotypic Histocompatibility Class I Antigen Associations on Trophoblast Cell Membranes: Relevance for Human Pregnancy1

Human placental syncytiotrophoblasts lack expression of most types of human leukocyte antigen (HLA) class I and class II molecules; this is thought to contribute to a successful pregnancy. However, the HLA class Ib antigens HLA-G, -E, and -F and the HLA class Ia antigen HLA-C are selectively expressed on extravillous trophoblast cells, and they are thought to play a major role in controlling feto-maternal tolerance. We have hypothesized that selective expression, coupled with the preferential physical association of pairs of HLA molecules, contribute to the function of HLA at the feto-maternal interface and the maternal recognition of the fetus. We have developed a unique analytical model that allows detection and quantification of the heterotypic physical associations of HLA class I molecules expressed on the membrane of human trophoblast choriocarcinoma cells, ACH-3P and JEG-3. Automated image analysis was used to estimate the degree of overlap of HLA molecules labeled with different fluorochromes. This approach yields an accurate measurement of the degree of colocalization. In both JEG-3 and ACH-3P cells, HLA-C, -E, and -G were detected on the cell membrane, while the expression of HLA-F was restricted to the cytoplasm. Progesterone treatment alone induced a significant increase in the expression level of the HLA-G/HLA-E association, suggesting that this heterotypic association is modulated by this hormone. Our data shows that the cell-surface HLA class I molecules HLA-G, -E, and -C colocalize with each other and have the potential to form preferential heterotypic associations.

Phenotypic characterization of mononuclear inflammatory cells following equine hydroxyapatite/collagen block grafting in rats

To measure the inflammatory changes associated with the implantation of an equine hydroxyapatite and collagen-containing block graft (eHAC block) in a rodent model system, an eHAC block graft was implanted subcutaneously in rats. Control groups included saline, turpentine oil, and human mineralized particulate allograft (hMPA). Animals were sacrificed and tissue samples obtained after three days, as well as after 1, 2, 4 and 8 weeks. A panel of immunologic probes was used to identify circulatory monocytic cells (ED1), resident mononuclear phagocytes (ED2), mononuclear phagocytes of lymphoid origin (ED3), expression of Ia antigen (OX6), T-cells (OX19), and B-cells (OX33). Immunocytochemical localization was performed and mononuclear cells localized with each immunologic probe counted. Rat sera obtained after eight weeks were used for nitrocellulose dot-blotting to assess circulating anti-equine immunoglobulins. Statistical analysis was performed using two-way analysis of variance, in conjunction with the Bonferroni correction to account for multiple comparisons. A transient increase in monocytes at 3 days and 1 week was observed in all groups, but was significantly higher in the turpentine control (P < 0.0001). A significant increase in the numbers of mononuclear cells detected with clones ED2 and ED3 was observed in specimens from the turpentine group, in contrast to the other groups in the 3 day to 4 week interval (P < 0.0001), as well as within all time periods (P < 0.0001). A statistically significant difference in numbers of ED3-positive cells was observed in the hMPA group compared to the saline and the eHAC block groups after one week (P < 0.0001). Significantly more OX6-positive cells were observed in the turpentine group, compared to other groups (3 days to 1 week; P < 0.0001). T-lymphocytes were essentially absent except for rats given turpentine (after 1 week). No B-lymphocyte response was found and none of the rats developed systemic anti-equine antibodies. These data indicate that a cellular immune response is not elicited following implantation with the eHAC block graft, which might serve as an alternative material for regenerative therapy.

Kinetics of Th17‐related cytokine expression in experimentally induced rat periapical lesions

Th17-related cytokines are essential factors in various pathological states, including inflammatory bone destruction. This study investigated the contribution of Th17-related cytokines to the progress of experimentally induced rat periapical lesions. Periapical pathoses were induced by unsealed exposure of the pulp chamber of the lower first molars. A variety of immunocompetent cells, including CD68(+) macrophages, Ia antigen(+) cells and TCRαβ(+) T cells, were observed in the lesions. The expression levels of Th17-related cytokines, IL-17 and IL-23, and of pro-inflammatory cytokines, IL-1β and IL-6, were significantly increased at 14 days (expansion stage) compared with normal periapical tissues. The expression levels of Foxp3, a regulatory T cell (Treg)-related gene, and of IL-10, an anti-inflammatory cytokine, were higher at 28 days (chronic stage) than at 14 days. These findings suggest that Th17-related cytokines may be primary contributors to the initiation of periapical bone destruction, and that lesion expansion may be regulated by anti-inflammatory mediators.

Immune privilege and alopecia areata

Hair follicles (HFs) are chiefly characterized by an absent or very low level of expression of MHC class Ia antigens, which is complemented by a number of factors, such as the local production of potent immunosuppressive agents, dysfunction of professional antigen-presenting cells and inhibition of natural killer cell activities. In the hair bulb, immune privilege (IP) is seen only in the anagen stage of HF cycling. The (‘noncycling’) bulge area of human scalp HFs also enjoy some relative, stably maintained IP. Hair bulge IP is constituted not only by factors of HF-IP, but also indoleamine 2,3-dioxygenase and CD200. A collapse of HF (hair bulb and hair bulge) probably plays an important role in the pathogenesis of two of the most common organ-specific autoimmune diseases, alopecia areata and cicatricial alopecia, respectively. Therefore, the therapeutic restoration of IP collapse promises to be a particularly effective future strategy for the treatment of these hair-loss diseases.

Microglia Activated with the Toll-Like Receptor 9 Ligand CpG Attenuate Oligomeric Amyloid β Neurotoxicity in in Vitro and in Vivo Models of Alzheimer’s Disease

Soluble oligomeric amyloid beta (oAbeta) 1-42 causes synaptic dysfunction and neuronal injury in Alzheimer's disease (AD). Although accumulation of microglia around senile plaques is a hallmark of AD pathology, the role of microglia in oAbeta1-42 neurotoxicity is not fully understood. Here, we showed that oAbeta but not fibrillar Abeta was neurotoxic, and microglia activated with unmethylated DNA CpG motif (CpG), a ligand for Toll-like receptor 9, attenuated oAbeta1-42 neurotoxicity in primary neuron-microglia co-cultures. CpG enhanced microglial clearance of oAbeta1-42 and induced higher levels of the antioxidant enzyme heme oxygenase-1 in microglia without producing neurotoxic molecules such as nitric oxide and glutamate. Among subclasses of CpGs, class B and class C activated microglia to promote neuroprotection. Moreover, intracerebroventricular administration of CpG ameliorated both the cognitive impairments induced by oAbeta1-42 and the impairment of associative learning in Tg2576 mouse model of AD. We propose that CpG may be an effective therapeutic strategy for limiting oAbeta1-42 neurotoxicity in AD.

Effect of carbachol on the expression of la on monocyte and lymphocyte apoptosis rate of the burned rats with delayed resuscitation

Objective To explore the changing trend of Ia on monocyte, lymphocyte apoptosis rate, TNF-α and IL-6 in abdominal aorta of burned rats with delayed resuscitation and the influence of application of carbachol on them. Methods Adult male Wistar rats were randomly divided into normal control group(n =8), scald group(n =48) and scald with carbachol treatment group(n =48). In latter two groups, rats were inflicted with 30% total body surface area (TBSA) full-thickness scald and delayed fluid resuscitation. All scald rats were sacrificed at the 6th hours or 1st, 2nd, 3rd, 7th, 14th day after scald, with 8 rats at each time point. Expression of Ia antigen on monocyte and lymphocyte apoptosis rate were determined by direct immunofluorescence on a flow cytometer, and TNF-α and IL-6 was measured by ELISA. Results Expression of la on monocyte was obviously lower than that of controls. The lowest levels were recorded on the 6th hours and 1st day after scald. Subsequently, Ia was elevated gradually, but still lower than that of normal rats(P <0. 01). After administration of carbachol, Ia expression was obviously promoted, compared with the simple scald group (P <0. 01). Lymphocyte apoptosis rate, TNF-α and IL-6 was higher than that of controls(P <0. 01). After administration of cavachol, , lymphocyte apoptosis rate and TNF-α and IL-6 was obviously down-regulated on the 6th hours, 1st day, 2nd day and 3rd day after scald injury, compared with the simple scald group (P < 0. 01 or 0. 05). Conclusion After severe burn with delayed fluid resuscitation, there is a low la expression, high lymphocyte apoptosis rate and increased releasing of proinflammatory cytokine. Immune function was suppressed. Carbacho] could improve the immune function of scald rats with delayed fluid resuscitation. Key words: CarbachoL/PD ; Bums/DT/IM

Serum-derived MHC class II molecules: Potent regulators of the cellular and humoral immune response

Soluble MHC antigens are detected in body fluids but their role and origin are still unclear. This study examined whether serum IA antigens, isolated from BALB/c mice (sIA d), could modulate the immune response. Specific purification procedures isolated intact IA molecules, which were thereafter applied to functional assays. Thus, sIA d were shown to stimulate spleen cell proliferation and the major target was identified to be the CD4 + cell population. Inhibition of the CD4 co-receptor using specific neutralizing antibodies destroyed the sIA d-mediated proliferative activity, while sIA d successfully antagonized surface IA d antigens for binding to anti-IA d antibody. Serum-IA d stimulated BALB/c versus C3H/HeN but not C3H/HeN versus BALB/c mixed lymphocyte reactions, while increasing responsiveness to Legionella pneumophila. However, sIA d displayed an inhibitory activity during the effector phase of the humoral response, since they inhibited the anti-DNP-specific IgM production to a DNP–HSA hapten–carrier system. Furthermore, sIA d molecules increased Th1/Th2 cytokines during the L. pneumophila stimulus, while decreasing IL-2, GM-CSF and increasing IL-4, IL-15 during the DNP–HSA stimulus. These results suggest that sIA d, following steps similar to surface class II antigen binding mechanisms, stimulate the initiation of a humoral or cellular immune response but rather inhibit the effector phase of the reactions, attributing thus soluble class II MHC antigens important immunomodulatory roles.

Modulation of murine host-versus-graft disease by anti-CD3 monoclonal antibody

BALB/c mice made tolerant to A/J alloantigens by neonatal injection of (A/J x BALB/c)F1 spleen cells develop a host-versus-graft (HVG) disease due to the activation of donor B cells by a subset of host alloreactive helper T cells. We have investigated the effects of a single neonatal injection of the 145-2C11 anti-mouse CD3 monoclonal antibody (MoAb) on the establishment of allotolerance and on the development of the immunopathological features of HVG disease. First, this treatment did not modify the specific anti-donor cytotoxic T lymphocyte (CTL) unresponsiveness or the persistence of circulating immunoglobulins bearing donor allotype. Second, the hyper IgE, the hyper IgG1 and the increased expression of Ia antigens on B cells found in untreated HVG mice were not observed after injection of the 145-2C11 MoAb. Likewise, treated mice displayed lower levels of anti-DNA IgG antibodies and less glomerular immune deposits as compared with untreated HVG mice. We conclude that the administration of the anti-CD3 MoAb did not interfere with the induction of allotolerance but exerts a pronounced inhibitory effect on the associated immunopathological syndrome.

Suppression of experimental allergic encephalomyelitis by intraventricular administration of interferon-gamma in Lewis rats

Experimental allergic encephalomyelitis (EAE) is an autoimmune inflammatory disease of the central nervous system (CNS) which causes paralysis. Several studies have reported the involvement of Ia antigen-expressing cells in the pathogenesis of EAE. Interferon-gamma (IFN-gamma) can induce Ia antigen expression on a wide range of cells. We examined the effect of IFN-gamma on EAE in Lewis rats. Systemically administered IFN-gamma did not change the disease course of EAE, whereas IFN-gamma applied locally into the ventricular system of the CNS resulted in complete suppression of clinical signs. Furthermore, we found that systemic administration of anti-IFN-gamma just prior to the onset of clinical symptoms resulted in a more severe disease course. We conclude that IFN-gamma is capable of exerting a suppressive action in EAE, possibly through induction of Ia antigen expression or through the induction of suppressive mechanisms locally in the CNS.

Regional cellular responses to intraperitoneal infection.

Leucocytes in different body compartments were examined in a murine intra-abdominal abscess model: (i) peripheral blood; (ii) peritoneal exudate; (iii) abscess wall; and (iv) abscess pus, with respect to their phagocytic ability, CR3 expression and Ia antigen expression (murine MHC antigen). The ability of serum or supernatant in each compartment to opsonize Staphylococcus aureus was also determined. Mice responded to caecal ligation and puncture (CLP) with systemic monocytosis, an increased amount of opsonins in peritoneal fluid and an increased phagocytosis in pus leucocytes. This increased phagocytic ability and CR3 expression both subsequently decreased. Monocyte/macrophage Ia expression was reduced in all measured compartments over time. In contrast, sham-operated animals, without an intra-abdominal abscess, responded to operation with an even greater increase in peritoneal exudate phagocytic ability and in monocyte/macrophage Ia expression in all compartments which was sustained beyond 1 week. Decreased peritoneal exudate cell and peripheral blood Ia was still present after 28 days in CLP animals, compared with both sham and normal animals (P less than 0.05, P less than 0.02, respectively). For all parameters, changes observed in peripheral blood did not reflect those present near the site of infection. Proper understanding of local or regional infection must take into account and ultimately alter these generally unappreciated changes in and about the actual site of infection.

Prostaglandin E1 suppresses macrophage infiltration and ameliorates injury in an experimental model of macrophage-dependent glomerulonephritis

Prostaglandin E1 (PGE1) suppresses macrophage infiltration and ameliorates injury in an experimental model of macrophage dependent glomerulonephritis. Macrophages are mediators of glomerular injury in models of proliferative glomerulonephritis. We have recently shown that macrophages in glomerulonephritis have low prostaglandin E2 (PGE) generation, and other evidence implicates eicosanoids as regulators of macrophage activation. Here we have studied in rats the effect of 15(s)-15-methyl PGE1 (M-PGE1) on accelerated nephrotoxic nephritis, a model of acute macrophage-dependent glomerular injury. M-PGE1 ameliorated proteinuria (day 4; 61 +/- 13 mg/24 h, n = 9; vehicle treated, 164 +/- 17 mg/24 h, n = 11; P less than 0.002) and glomerular hypercellularity; quantification of infiltrating macrophages by isolating glomerular cells showed reduction in the numbers of macrophages (44 +/- 9/glomerulus; vehicle treated, 119 +/- 15/glomerulus; P less than 0.02) with inhibition of Ia antigen expression on infiltrating macrophages (8 +/- 5%; vehicle treated 25 +/- 4% P less than 0.05). Glomerular binding of nephrotoxic globulin and levels of autologous antibodies were not affected by M-PGE1. Thus the mechanism of suppression involves inhibition of macrophage accumulation and activation. M-PGE1 administered to normal rats did not affect numbers of resident leucocytes (12.6 +/- 1.5/glomerulus; vehicle treated, 13.2 +/- 1.3/glomerulus) or alter Ia antigen expression (4.1 +/- 0.2 Ia + cells/glomerulus; vehicle treated, 3.9 +/- 0.6/glomerulus). This study suggests a therapeutic role for PGE1 in this type of glomerulonephritis, and has implications for the pathophysiology of macrophage-mediated inflammation.

Etiology of sperm immunity in women

Sperm immunity in females can reduce the likelihood of natural conception, and sperm antibodies from female sera have been shown to inhibit IVF in humans and in several animal models. The etiology of sperm immunity in human females is unknown, but several possible mechanisms have been proposed, including cross-reactivity with microbial antigens and interferon gamma-mediated potentiation of the antisperm immune response in women whose male partners have sperm autoantibodies in their semen. This article reviews these ideas and postulates a novel hypothesis based on the potential for the generation of anti-idiotype antibodies in women whose partners have sperm antibodies in their semen.