Induction of Th2 cell differentiation by cognate interaction of CD4 memory T cells

Th2 cell differentiation can be induced from human CD4 memory T cells by priming with anti-CD28 without engagement of the TCR. To test whether CD28 mediated Th2 differentiation from memory T cells was an effect of a particular anti-CD28 mAb, Th2 differentiation was assessed after priming of purified CD4 memory T cells with transfected myeloma cells expressing human CD80 and/or CD86. Whereas the mock control did not induce Th2 differentiation, priming in the presence of myeloma cells expressing CD80, CD86 or CD80 and CD86 significantly increased Th2 frequencies. Thus, Th2 differentiation from memory T cells can be induced by engaging CD28 with its natural ligands, CD80 and/or CD86. We next evaluated the possibility that activated T cells might prime bystander T cells for Th2 differentiation. CD4 memory T cells were activated with mAbs to CD3 and CD28 for five days. Flow cytometric analysis revealed that in contrast to resting T cells, activated T cells expressed CD80, however, at a low level. CD80 expressing T cells were fixed and cocultured with freshly isolated, syngeneic, CD4 memory T cells for five days in the presence or absence of exogenous IL-4, but without additional stimulatory signals. For control, priming was performed with fixed syngeneic T cells that were freshly isolated and, thus, negative for CD80. Priming with fixed, non-activated syngeneic T cells did not induce Th2 differentiation, even in the presence of exogenous IL-4. In marked contrast, priming with fixed activated T cells induced significant Th2 differentiation. This effect was dependent on exogenous IL-4, suggesting that the low levels of CD80 expressed on activated T cells were not sufficient to induce IL-4 transcription. However, the data indicate, that Th2 differentiation might be induced from bystander T cells by recently activated T cells through cognate T-T-cell interaction involving CD28. TCR independent generation of Th2 effectors might provide a way to control Th1 dominated cellular inflammation.