TA Cells Research Articles

Strategies of epithelial repair: modulation of stem cell and transit amplifying cell proliferation.

Using double labeling techniques, we studied the replication of corneal epithelial stem cells that reside exclusively in the limbal zone, and their progeny transit amplifying cells. We show that corneal epithelial stem cells can be induced to enter DNA synthesis by wounding and by TPA. We demonstrate the existence of a hierarchy of TA cells; those of peripheral cornea undergo at least two rounds of DNA synthesis before they become post-mitotic, whereas those of central cornea are capable of only one round of division. However, the cell cycle time of these TA cells can be shortened and the number of times these TA cells can replicate is increased in response to wounding. These results thus demonstrate three strategies of epithelial repair: (i) stem cell replication, (ii) the unleashing of additional rounds of cell proliferation that remain as an untapped reserve under normal circumstances, and (iii) enhancement of TA cell proliferation via a shortening of the cycling time.

Strategies of epithelial repair: Modulation of stem cell and transit amplifying cell proliferation

ABSTRACT Using double labeling techniques, we studied the replication of corneal epithelial stem cells that reside exclusively in the limbal zone, and their progeny transit amplifying cells. We show that corneal epithelial stem cells can be induced to enter DNA synthesis by wounding and by TPA. We demonstrate the existence of a hierarchy of TA cells; those of peripheral cornea undergo at least two rounds of DNA synthesis before they become post-mitotic, whereas those of central cornea are capable of only one round of division. However, the cell cycle time of these TA cells can be shortened and the number of times these TA cells can replicate is increased in response to wounding. These results thus demonstrate three strategies of epithelial repair: (i) stem cell replication, (ii) the unleashing of additional rounds of cell proliferation that remain as an untapped reserve under normal circumstances, and (iii) enhancement of TA cell proliferation via a shortening of the cycling time.

Dissociation of thyrotropin receptor function and thyrotropin dependency in rat thyroid tumour cell lines derived from FRTL-5.

Spontaneously transformed somatic thyrocyte mutants, FRTL-5/TA and FRTL-5/TP, are thyrotropin (TSH) independent for growth and show loss of the thyroid-specific phenotype, with absent thyroglobulin and thyroid peroxidase gene expression. To investigate the role of TSH-receptor (TSH-R) activation in rat thyroid growth and function, binding of TSH and TSH-induced cAMP production were measured in intact cells under identical assay conditions. TSH binding did not differ in terms of affinity and receptor number and presence of 5.6 kb and 3.3 kb mRNA rat TSH-R transcripts was determined in all variants. By contrast, basal cAMP was 11-fold lower in FRTL-5/TA and 6-fold lower in FRTL-5/TP than in wild-type FRTL-5 (1.1 +/- 0.4; P < 0.01). Maximal cAMP production was similar between wild-type and cell variants and stimulation by bovine, rat and recombinant human TSH revealed normal activation patterns. Therefore, a dissociation was present between the loss of TSH control on growth and function, and the presence of a normally functioning TSH-R. Subsequent to TSH incubation FRTL-5/TP and FRTL-5/TA cells showed a different expression pattern of TSH-R and the proto oncogenes c-myc and fos than FRTL-5 wild-type. The data indicated that the cause of the TSH-independency is located down-stream of the cAMP cascade, influencing genes that control the expression of cell cycle-related proto-oncogenes and thyroid-specific genes.

Distribution of leukocyte subpopulations in the human corpus luteum

Cytokines, as secreted products of leukocytes, have roles in many organs of the body via paracrine or autocrine mechanisms. In the present study, we demonstrate by immunocytochemistry the leukocytes present in the human corpus luteum in order to investigate further the relationship between leukocytes, cytokines and corpus luteum function. Ten intact corpora lutea were collected from female patients who had no apparent ovarian disease. The mean age of these patients was 37 years (range 23-55 years). Frozen and paraffin sections were subjected to analysis using monoclonal antibodies which were specific to leukocyte marker antigens. The results showed that there are macrophages, cells positive for leukocyte common antigen (LCA), T lymphocytes including T helper/inducer (T4) cells, T cytotoxic/suppressor (T8) cells and activated T (Ta) cells (interleukin-2 receptor-positive cells), monocytes and natural killer (NK) cells but not B lymphocytes present in the human corpus luteum. The distribution of the leukocytes present in the different parts of the corpus luteum was found to be in the order: theca-luteal area greater than loose connective tissue area greater than granulosa-luteal area. Macrophages and T lymphocyte subsets comprised the main components of the total leukocytes in the human corpus luteum. Ta cells were only localized in the loose connective tissue of the corpus luteum. In most cases, macrophages, LCA cells and T4 cells tended to be situated in a single cell layer on the edge of the theca-luteal area and surrounding the granulosa-luteal area. These results suggest that the leukocytes may act to a greater extent in the theca-luteal area than in the granulosa-luteal area.(ABSTRACT TRUNCATED AT 250 WORDS)

T Cells Regulate the IgM Antibody Response of BALB/c Mice to Dextran B1355

The IgM antibody response of BALB/c mice to bacterial (Leuconostoc) dextran B1355 is influenced in a positive and negative manner by regulatory CD4 + and CD8 + T cells, respectively. Treatment with concanavalin A (Con A) at the time of immunization or 2 days later caused suppression and enhancement of the antibody response, respectively. Priming of mice with a sub-immunogenic dose of dextran resulted in profound suppression upon subsequent immunization 3 days later. None of these effects were demonstrable in athymic mice. Transfer of T cells from mice primed 18 h previously with a subimmunogenic dose of dextran suppressed the antibody response in immunized recipients; such suppression was abolished by the treatment of transferred cells with anti Thy 1.2 or anti Lyt 2.2 (CD8) antibody in the presence of complement. By contrast, the transfer of T cells from mice, which had been given an immunogenic dose of dextran 4 days previously, increased the antibody response in immunized recipients; such enhancement was abolished by treating transferred cells with anti Thy 1.2 or anti L3T4 (CD4) antibody in the presence of complement. These findings indicate that the immune response to dextran B1355 is regulated by CD4 + T-amplifier cells (Ta cells) and by CD8 + T-suppressor cells (Ts cells) which are activated during the course of a normal antibody response.

T-cell modulation of the antibody response to bacterial polysaccharide antigens

Pretreatment of mice with subimmunogenic doses of meningococcal polysaccharide (MP), Pseudomonas aeruginosa lipopolysaccharide (PA), or Streptococcus mutans polysaccharide (SM) resulted in suppression of antibody response. The transfer of putative suppressor T cells (Ts cells) from donor mice primed with a subimmunogenic dose of MP to naive recipients at the time of immunization with MP substantially reduced the magnitude of the antibody response. Also, the infusion of B cells taken from animals immunized with either MP or PA suppressed the antibody response of naive recipients to MP or PA, respectively, relative to controls, suggesting that Ts cells respond to determinants on immune B cells. We observed that the injection of concanavalin A or phytohemagglutinin (two lectins known to augment the activity of amplifier T cells [Ta cells]) 2 days postimmunization enhanced the antibody response to MP and SM. In addition, Ta-cell activity was transferred to naive animals by using spleen cells. Although the administration of phytohemagglutinin at the time of immunization with MP also resulted in increased antibody response, the injection of concanavalin A simultaneous with immunization resulted in a suppression of the antibody response to MP. Although Ts cells generated in response to pneumococcal polysaccharide type III were found to respond to monoclonal antibody Ly-m22, Ta cells responded to monoclonal antibodies L3T4 and Ia but not to Ly-m22. These studies suggest that Ta and Ts cells can modulate the antibody response to MP, SM, and PA in a positive and negative manner, respectively.

Fc-specific suppressor T cells.

BALB/c mice bearing IgA-secreting plasmacytomas exhibit large numbers of Thy-1+, Ly-2+ lymphocytes with surface membrane receptors specific for IgA (Ta cells) (1). These lymphocytes have several characteristics of immunoregulatory T cells (2) and develop in response to the high circulating levels of polymeric IgA as evidenced by: a) their failure to develop in mice bearing IgA non-secreting variant plasmacytomas (1) and (b) their occurrence in normal mice infused daily with high concentrations of polymeric IgA (3). When suppressor Ta cells were transferred to orallyimmunized mice the recipient mice exhibited a marked suppression of the IgA component, but not the IgM or IgG components, of an immune response to an orally administered antigen (4). These findings identify an immunoregulatory circuit in which IgA secreting cells are simultaneously effector cells and regulatory cells. Secreted IgA antibody, in addition to its antigen-specific effector function, can provide an inductive signal for the IgA-binding suppressor T cells which in turn can inhibit further IgA secretion. Enhanced expression of IgA receptors on suppressor T cells requires polymeric forms of IgA which suggests that IgA-Fc receptor cross-linking is a necessary step in the induction process. Under physiological conditions it may be that receptor crosslinking is mediated by the polyvalent arrays of Fc determinants that occur in immune complexes.

Lipid Modulation of Mammary Tumor Cell Cytolysis: Direct Influence of Dietary Fats on the Effector Component of Cell-Mediated Cytotoxicity&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;

For understanding the mechanism by which fatty acids promote mammary tumor growth, experiments were designed to determine the influence of dietary fat concentration and saturation on both effector (Ef) and target (Ta) cells in an allogeneic antitumor cell-mediated immune response. Exposure of cytotoxic T-lymphocytes (CTL) to different fatty acids led to significant changes in the subsequent cytolytic capacity of these cells after both primary and secondary immunization. An increase in both saturated (SF) and polyunsaturated (PUF) fats led to decreased cytotoxic function after primary immunization. After a secondary challenge, the suppressive influence of SF was significantly greater than that of PUF, compared to that of the control diet containing essential fatty acids as the only fat source. This response was mediated by a direct effect on the CTL and not through an increase in suppressor or a decrease in Ef or helper cell frequency. In contrast, manipulation of the fatty acid environment of the Ta mammary tumor cells in vivo or in vitro had no significant effect on their susceptibility to lymphocyte-mediated cytotoxicity. Therefore, dietary fats may mediate their effect by a direct influence on the immunocompetent lymphocyte and not on the Ta mammary tumor cell.

T cell regulation of B cell activation: MHC-restricted T augmenting cells enhance the B cell responses mediated by MHC-restricted cloned T helper cells.

The present studies demonstrated that unprimed populations of Lyt-1+2- T cells are able to augment the responses generated by optimal numbers of antigen-specific and MHC-restricted cloned TH cells. The TA cells function early in the course of B cell responses. Responses mediated by (A X B)F1 (B + accessory) cells and parentA restricted cloned TH cells are augmented by TA cells from (A X B)F1 leads to parentA radiation bone marrow chimeras, but not by TA cells from (A X B)F1 leads to parentB chimeras. Thus, TA cell activation and function are MHC-restricted, but this restriction is not related to recognition of genotypically expressed B cell and/or accessory cell MHC products alone. Rather, TA cell function is intimately related to the MHC-restricted interaction between TH cells and responding (B + accessory) cells. Specifically, it was shown that TH cell interaction with B cells via an MHC-restricted and carrier-hapten-linked pathway is required for the function of TA cells expressing the same MHC restriction. Moreover, neither MHC homology nor TH cell recognition of MHC determinants on TA cells is required for TA cell function, and the activity of TA cells is not demonstrably influenced by non-MHC genes. It was further demonstrated that the function of cloned TH cells in B cell activation consists of at least two distinct components, one is radiosensitive and the other is radioresistant. TA cells are able either to replace the radiosensitive function of cloned TH cells directly or to bypass this requirement through an alternative pathway.

Density distribution profiles of T cells: TM, TG and TA cells and response patterns in autologous versus allogeneic MLRs.

Discontinuous Percoll gradients have been used to obtain selected human peripheral blood T lymphocytes without having to resort to interactions with immune complexes in the fractionation of Tm, Tg and Ta cells. Here, we could show that Ta cells represent a heterogeneous population with no distinct density profile, in contrast to light (Tg) and heavy (Tm) cells. Enriched, heavy Tm cells could be shown to be excellent responders in allogeneic MLR while failing to react in autologous MLR. In contrast, T cells of light density preferentially respond in autologous compared with allogeneic MLR.

Requirement for properdin in hemolysis of human erythrocytes treated with tannic acid.

Summary1) The hemolysis of normal human erythrocytes exposed to appropriate dilutions of tannic acid by human serum, requires the properdin system, which consists of properdin, complement, and magnesium. 2) Similarities and differences are pointed out between the properties and mechanism of hemolysis of tannic-acid-treated cells and erythrocytes from patients with paroxysmal nocturnal hemoglobinuria. 3) While the hemolysis of TA cells is suitable for the assay of purified properdin it is not reliable for the quantitative measurement of properdin in serum.