REQUIREMENT OF A 2ND SIGNAL FROM ANTIGEN-PRESENTING CELLS IN THE CLONAL DELETION OF IMMATURE T-CELLS

The role of antigen presenting cells (APC) in T cell clonal deletion w as investigated by culturing murine thymic lymphocytes with the supera ntigen staphylococcal enterotoxin B (SEB) in the absence or presence o f APC. As the APC, we used B lymphoma cell lines A20.2J and BAL17.2, b oth expressing MHC class II antigens at high levels. SEB reactive V(be ta)8(+) cells were deleted only when A20.2J cells were used as APC. By using thymocytes from transgenic mice carrying a TCR beta chain trans gene, it was further shown that the deletion occurred at the CD4(+)CD8 (+) stage. The other cell line, BAL17.2, failed to induce clonal delet ion, although this cell line was able to stimulate the proliferative r esponse of SEB-primed T cells. The activity of A20.2J cells to induce clonal deletion was completely abolished by fixation with paraformalde hyde, whereas the same treatment kept the ability of this cell line to induce the proliferative response of non-primed as well as SEB-primed T cells. It was further shown that the deletion was abolished by the addition of anti-MHC class II but not anti-B7 mAb in the culture. Thes e results provided explicit evidence that a signal(s) from APC, which is distinct from that required for primary or secondary proliferative response of mature peripheral T cells, is involved in clonal deletion of thymic immature T cells.