MONOCYTE-INDEPENDENT T-CELL ACTIVATION BY SIMULTANEOUS BINDING OF 3 CD2 MONOCLONAL-ANTIBODIES (D66+T11.1+GT2)

Mitogenic pairs of CD2 mAb typically transduce activation/proliferatio n signals within T cells. However, complementary signal(s) provided by accessory cells are required to induce T cell proliferation. We show here that a particular combination of three CD2 mAb, D66 + GT2 + T11.1 , leads to the proliferation of highly purified human T lymphocytes, w ithout other complementary signal(s). The CD2 triplet was able to indu ce CD4(+) and, to a lesser extent, CD8(+) cells to proliferate. Intere stingly, the so-called ''naive'' T cells (CD45RA(+)) were strongly sti mulated, but more immature cells, such as thymocytes, were not. The pr oliferative response induced by the CD2 triplet was entirely mediated by the IL-2 autocrine pathway, as shown by the complete inhibition wit h anti-IL2 Ab. T cells stimulated with the CD2 triplet were also able to secrete TNF alpha. We found no evidence for an unusual secretion of cytokines that might explain the lack of requirement of complementary signal(s). As high as it was, the proliferation induced by the CD2 mA b triplet could be further increased by the addition of IL-1, and this proliferative fraction could be inhibited by antibodies against TNF a lpha. The CD2 mAb triplet increased [Ca2+](i), while mitogenic CD2 mAb pairs needed the presence of a cross-linking agent. Thus, our data sh ow that T cells can be activated to fully proliferate by this particul ar CD2 pathway, in the absence of accessory signal(s). (C) 1995 Academ ic Press, Inc.