Role of interleukin 6 for differential responsiveness of naive and memory CD4+ T cells in CD2-mediated activation

The present study was undertaken to elucidate different requirements for CD2-mediated activation of naive (CD45RO-) and memory (CD45RO+) CD4+ T cells. A mitogenic combination of anti-CD2 (antiT112 and antiT113) mAbs could effectively induce the proliferation of memory CD4+ T cells even in the absence of monocytes. In marked contrast, naive CD4+ T cells did not disclose any proliferative responses to anti-CD2 mAbs, when monocytes were absent in culture. This differential responsiveness of naive and memory CD4+ T cells appeared to be related largely to a difference in I1,6-producing ability between both populations. I1r6 among monocyte-derived cytokines could correct unresponsiveness of naive CD4+ T cells to anti-CD2 stimulation. Unlike naive CD4+ T cells, memory CD4+ T cells produced IIr6 by themselves, with its mRNA being expressed on anti-CD2 stimulation. Anti-IIr6R mAb significantly inhibited proliferation of memory CD4+ T cells seen in the anti-CD2-stimulated cultures without monocytes, indicating the involvement of their own production of Ilr6 in CD2-mediated activation. The results suggest an essential role of 1176 for triggering of CD4+ T cells via the CD2 molecule. The 50-kD CD2 molecule, originally defined as the sheeperythrocyte receptor, is one of the earliest T cell differen-tiation antigens to appear on developing thymocytes befor