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MRL-lpr mice and their congenic counterparts MRL- + spontaneously develop an autoimmune disease that resembles systemic lupus erythematosus in humans. The two strains, although congenic, differ by a considerable number of disease parameters, reflecting the expression of the lpr autosomal recessive gene. One paradox that has developed out of the work utilizing the congenic mice is that the gene responsible for lymphoproliferation also appears to be responsible for the inability of T cells to respond to proliferative signals in vitro. In this paper we investigated a possible lpr gene-encoded macrophage defect in these mice. It was found, however, that both the MRL- + and MRL-lpr mice failed to divide in response to Con A, the lack of division correlating with an inability to secrete the growth promoter interleukin-2. In MRL- + mice and young MRL-lpr mice this non-responsiveness was corrected by the addition of normal CRA PEC. The defect could not be explained by a failure of M RL- + or M RL-lpr peritoneal exudate cells to quantitatively or qualitatively provide a source of interleukin-1 to Con A-activated T cells or by the possibility that the peritoneal exudate cells were blocked in their function by the presence of sera-derived autoantibodies and/or immune complexes on their membranes. We postulate that the inability of T cells to proliferate in MRL congenic mice can be explained by two defects: (i) the failure of antigen-presenting cells in MRL- + and MRL-lpr to provide the necessary signals to immunocompetent T cells, this defect not being associated with the lpr gene, and (ii) the lpr gene controlled outgrowth of a unique T-cell population that cannot respond in our assay system. [ABSTRACT FROM AUTHOR]

The CD31 molecule is a leucocyte-surface glycoprotein of 130 kDa with homology to the immunoglobulin gene superfamily. In this study we report on the expression of CD31 on human T cells and demonstrate that it subdivides peripheral blood T lymphocytes into two novel subsets. CD31 is expressed by 38% of CD3+ lymphocytes. About 85% of CD313+ T cells display the CD45RA phenotype, 35% the CD45RO phenotype, 24% the CD4 phenotype and 72% the CD8 phenotype. There is also a correlation between CD31 expression and CD45RA expression in cord blood T cells; 89% of CD33+ cord blood cells express CD31, and most of them have the CD45RA phenotype. A discrepancy was found with thymocytes, which are positive for CD31 but negative for CD45RA. Stimulation of human T cells leads to down-regulation of CD45RA, while CD31 continues to be expressed. In functional studies, CD31 antibody binding to T lymphocytes does not lead to mobilization of intracellular calcium, proliferation or modulation of T-cell proliferation. [ABSTRACT FROM AUTHOR]

Experiments have been carried out in vitro and in vivo to determine to what extent CD8+ T cells in the rat can function independently of any helper activity from CD4+ cells. We have identified the culture conditions required for the autonomous proliferation of CD8+ T cells in the rat mixed leucocyte culture (MLC) and in particular have studied both the kinetics of the response and the effect of replacing the homologous serum, used in our previous MLC experiments, with fetal calf serum (FCS). The results obtained using FCS show that, early in the MLC, CD8+ Tails proliferate at a comparable rate to the CD4+ subset but that, within 48-72 hr, the proliferation rate of the CD8+ cells ceases to increase with time. In contrast, the proliferation of the CD4+ T cells appears to be limited only by the exhaustion of the culture medium. The results also show that the proliferative responses of both CD4+ and CD8 + T cells are inhibited in homologous serum but that it is the CD8+ subset that is more affected. When CD8+ T cells, in homologous serum, are co-cultured with irradiated CD4+ T cells the proliferative activity is increased, indicating that the helper activity of the CD4+ T cells can over-ride the inhibitory effect of the serum. In vivo we have compared the abilities of injected CD4+ and CD84 T cells to mediate rejection of skin allograft's on nude rats. Grafts were rejected more rapidly on recipients of low doses of CD4+ T cells than on rats given 200 times as many CD8+ T cells. Thoracic duct lymphocytes (TDL) obtained 5 weeks after CD8+ T-cell injection always contained a population of CD4+ T cells, even when the injected CD8+ T-cell inoculum contained less than 0. 1 % CD44 cells as contaminants. Evidence was obtained that these CD4+ T cells found in TDL displayed alloreactivity in MLC. Further, the intentional injection of very low doses of CD4+ cells led, after 5 weeks, to frequencies of CD4+ T cells, in thoracic duct lymph, equal to that obtained by the injection of 200 times as many cells of the same phenotype. It appears that, in T-cell-deficient rats, CD4+ cells can expand over 2000 times in a few weeks. Such expansion may explain the relatively slow rejection of skin allografts observed in these experiments when nude rats were injected with putatively pure populations of CD8+ T cells. Taken together the data do not support the view that rat CD8+ T cells display significant autonomy in vivo but they do show a generally low level of alloreactivity in vitro. In contrast, our results stress that CD4+ T cells are uniquely potent in their ability to provide helper activity for CD8+ T cells in vitro and to mediate graft rejection in vivo. Our data are therefore not consistent with the concept that the two subsets are functionally equivalent and differ only with respect to the class of MHC antigen to which they are responsive. [ABSTRACT FROM AUTHOR]