TCR- and IL-1-mediated co-stimulation reveals an IL-4-independent way of Th2 cell proliferation.

Previously, it has been shown that Th1 cells, when triggered solely via their TCR, are blocked from proliferation in response to IL-2. Herein, we describe a similar characteristic for T^ cells In that immobilized mAb directed to the TCR blocked proliferation of Th2 cells in response to IL-4. This 'prollferatlve block' was observed in all four Th2 cell clones tested, but not In a subllne of one of the clones which has been cultured In vitro for several years. Addition of IL-1 neutralized the proliferatlve block In all four Th2 cell clones. Surprisingly, blocking experiments with slL-4R and anti-IL-4 mAb revealed that In three out of four T^ cell clones this effect of IL-1 was IL-4independent and could also not be blocked by cyclosporln A (CsA). In contrast, the proliferation of one Th2 cell clone In response to the TCR- and IL-1-mediated signals was indeed Inhibited by sIL4R, antML-4 mAb and CsA. Thus, our data illustrate that In addition to the well-known IL-4dependent proliferation, there also exists an IL-4-lndependent, IL-1-mediated way of Th2 cell proliferation.