Lymphoid environment limits superantigen and antigen-induced T cell proliferation at high precursor frequency

After superantigen challenge a significant proportion of superantigen-react ive T cells remain undivided. We provide evidence that the lymphoid environ ment 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 frequen cy of superantigen-reactive T cells was low (1%), intermediate (15%) or hig h (30-100%) by transferring fluorescently labeled cells into different reci pients. When the frequency was low, practically all the reactive T cells en tered 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 al ter the percentage of undivided cells but induced a further decrease in the number of cell divisions. Interestingly, the observations made with supera ntigens were confirmed with peptide antigen and TCR-transgenic mice. Moreov er, in vivo and in vitro data suggest that dendritic cells are the most lik ely candidates in limiting T cell proliferation in the lymphoid environment . In conclusion, we show that the availability of APC in the lymphoid envir onment can quantitatively limit T cell priming.