Lymphoid environment limits superantigen and antigen-induced T cell proliferation at high precursor frequency.
After superantigen challenge a significant proportion of superantigen-reactive T cells remain undivided. We provide evidence that the lymphoid environment limits T cell proliferation in the secondary lymphoid organs when the frequency of superantigen reactive T cells is unusually high. We monitored T cell proliferation and the percentage of undivided cells when the frequency of superantigen-reactive T cells was low (1%), intermediate (15%) or high (30-100%) by transferring fluorescently labeled cells into different recipients. When the frequency was low, practically all the reactive T cells entered cell cycle and proliferated maximally. At intermediate frequencies a large proportion of reactive T cells did not enter cell cycle and the whole population divided less. A further increase in reactive T cells did not alter the percentage of undivided cells but induced a further decrease in the number of cell divisions. Interestingly, the observations made with superantigens were confirmed with peptide antigen and TCR-transgenic mice. Moreover, in vivo and in vitro data suggest that dendritic cells are the most likely candidates in limiting T cell proliferation in the lymphoid environment. In conclusion, we show that the availability of APC in the lymphoid environment can quantitatively limit T cell priming.
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne Epalinges, Switzerland.
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Attinger
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MacDonald
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Acha-Orbea
D019264:Adoptive Transfer; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology; D002478:Cells, Cultured; D004768:Enterotoxins / Q000276:immunology; D005452:Fluoresceins / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000502:physiology; D013234:Stem Cells / Q000276:immunology; D013388:Succinimides / Q000737:chemistry; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation
C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D000941:Antigens; D004768:Enterotoxins; D005452:Fluoresceins; D005456:Fluorescent Dyes; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013388:Succinimides; D018089:Superantigens; C031818:enterotoxin B, staphylococcal