ACCESSORY SIGNALING BY B7-1 FOR T-CELL ACTIVATION-INDUCED BY ANTI-CD2- EVIDENCE FOR IL-2-INDEPENDENT CTL GENERATION AND CSA-RESISTANT CYTOKINE PRODUCTION

Resting T cells can be activated by selected pairs of anti-CD2 MoAb. A ctivation is dependent on the presence of accessory cells, which can b e replaced by either anti-CD28, or by the combination of IL-1 beta and IL-6. The present study was undertaken to investigate accessory signa lling by B7-1, the natural ligand of CD28, in this pathway of T cell a ctivation. 3T6 mouse fibroblasts were transfected with human B7-1 and used as accessory cells in cultures of purified resting human T cells. In the presence of a stimulating pair of anti-CD2 MoAb, T cell prolif eration, production of cytokines (IL-2, IL-4, IL-10, GM-CSF, IFN-gamma and TNF-alpha), and generation of cytotoxic T lymphocytes were all su pported by B7-1(+) 3T6 cells but not by control 3T6 cells. Blocking st udies with anti-IL-2 + anti-IL-2R MoAb revealed both IL-2-dependent an d IL-2-independent CTL generation after B7-1-mediated costimulation. M oreover, a partial or complete resistance to inhibition with CsA was o bserved for IL-2 production and CTL generation respectively in the pre sence of the costimulatory signal derived from B7-1 - CD28 interaction . Anti-CD2 MoAb with B7-1 costimulation could directly induce prolifer ation, IL-2 production and generation of CTL activity in highly purifi ed CD8(+) T cells without the help of CD4(+) T cells. We conclude that CD28 ligation with the natural ligand B7-1 provides a strong accessor y signal for CD4 and CD8 cell activation through CD2.