Accessory Signalling by B7-1 for T Cell Activation Induced by Anti-CD2: Evidence for IL-2-Independent CTL Generation and CsA-Rcsistant Cytokine Production

Resting T cells can be activated by selected pairs of anti-CD2 MoAb. Activation is dependent on the presence of accessory cells, which can be replaced by either anti-CD28, or by the combination of IL-1β and IL-6. The present study was undertaken to investigate accessory signalling by B7-1, the natural ligandof CD28, in this pathway of T cell activation. 3T6 mouse fibrobiasts 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 proliferation, production of cytokines (IL-2, IL-4, IL-10, GM-CSF, IFN-α and TNF-α), and generation of cytotoxic T lymphocytes were all supported by B7-l(+) 3T6 cells but not by control 3T6 cells. Blocking studies with anti-IL-2 + anti-IL-2R MoAb revealed both IL-2-dependent and IL-2-independent CTL generation after B7-1 -mediated costimulation. Moreover, a partial or complete resistance to inhibition with CsA was observed for IL-2 production and CTL generation respectively in the presence of the costimulatory signal derived from B7-1 - CD28 interaction. Anti-CD2 MoAb with B7-1 costimulation could directly induce proliferation, IL-2 production and generation of CTL activity in highly purified CD8⁺ T cells without the heip of CD4⁺ T cells. We conclude that CD28 ligation with the natural ligand B7-1 provides a strong accessory signal for CD4 and CD8 cell activation through CD2.