Trans-stimulation of T cells: characterization of targets and involvement in loss of alloreactivity.
The rapid loss of alloreactivity within populations of antigen-primed, in vitro propagated T cells cannot be explained by the appearance of suppressor cells nor by the dilution effect of the proliferative antigen-specific T cells alone. The involvement of trans-stimulation in loss of alloreactivity, i.e. the recruitment of non-antigen-specific T cells into proliferation in an antigen-dependent and specific fashion, was assessed. Susceptibility to trans-stimulation was found to correlate directly with state of activation at the outset of assay. Large T cells (low buoyant density) but not small T cells (high buoyant density) are susceptible to trans-stimulation. Moreover, in vitro pre-activation of small T cells by mitogen confers susceptibility to trans-stimulation. Analysis of the alloreactivity in Percoll fractions of antigen-primed lymph node T cells revealed activity in both large- and small-T-cell fractions with some enrichment in the latter. The small T cells, refractive to trans-stimulation, are diluted out of the population within the early weeks of antigen-mediated in vitro propagation, accounting for a rapid loss of considerable alloreactivity. The loss of all detectable alloreactivity within antigen-selected populations suggests that the state of activation conferring sensitivity to trans-stimulation must be maintained, and that neither the antigen nor the culture conditions employed met this requirement.
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Petit
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Julius
D000818:Animals; D002478:Cells, Cultured; D000939:Epitopes / Q000276:immunology*; D005260:Female; D007519:Isoantigens / Q000276:immunology*; D007700:Kinetics; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*
D000939:Epitopes; D007519:Isoantigens