ARE CD4(+) T(H)1 CELLS PRO-INFLAMMATORY OR ANTIINFLAMMATORY - THE RATIO OF IL-10 TO IFN-GAMMA OR IL-2 DETERMINES THEIR FUNCTION

Human CD4(+) T cells have, like their murine counterparts, been classified on the basis of their cytokine profile, T(h)1 cells produce IL-2 and IFN-gamma, but little or no IL-4, T(h)2 cells produce IL-4 but not IFN-gamma or IL-2, and T(h)0 produce IL-2, IL-4 and IFN-gamma. As IL-2 is the most potent T cell growth factor and IFN-gamma is the strongest activator of macrophages it is not surprising that CD4(+) T(h)1 cells are considered to be pro-inflammatory. However, unlike results in the mouse, where IL-10 is only produced by T(h)2 cells, human IL-10 is produced by T(h)0, T(h)1 and T(h)2 cells. Hence some human T(h)1 cells are capable of producing both pro-inflammatory (IL-2, IFN-gamma) and anti-inflammatory (IL-10) cytokines, therefore the function of these cells may not be accurately encapsulated by the 'T(h)1' terminology. We thus investigated the correlation of cytokine production and function in human CD4(+) T(h)1 clones. Cytokine production (IL-2, IFN-gamma I, IL-10) was measured in supernatants by ELISA after stimulation with solid-phase anti-CD3, The capacity of these supernatants to activate or inhibit T cell proliferation or LPS induced TNF-alpha production by monocytes was assessed. The ratio of IL-2/IL-10 or IFN gamma/IL-10 was of critical importance in determining the function of the supernatants. The inhibitory effects were verified to be due to IL-10, as they were neutralized by anti-IL-10 mAb. These results indicate that human CD4(+) T-h1 T cells are heterogeneous in their function, some being pro-inflammatory and others anti-inflammatory. Thus the 'T(h)1' classification with human T cells does not necessarily imply a pro-inflammatory function.