TCR- and IL-1-mediated co-stimulation reveals an IL-4-independent way of T(h)2 cell proliferation

Abstract

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