Are CD4+ Th1 cells pro-inflammatory or anti-inflammatory? The ratio of IL-10 to IFN-γ or IL-2 determines their function

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Abstract
Human CD4+ T cells have, like their murine counterparts, been classified on the basis of their cytokine profile. Th1 cells produce IL-2 and IFN-γ, but little or no IL-4. Th2 cells produce IL-4 but not IFN-γ or IL-2, and Th0 produce IL-2, IL-4 and IFN-γ. As IL-2 is the most potent T cell growth factor and IFN-γ is the strongest activator of macrophages it is not surprising that CD4+ Th1 cells are considered to be pro-inflammatory. However, unlike results in the mouse, where IL-10 is only produced by Th2 cells, human IL-10 is produced by Th0, Th1 and Th2 cells. Hence some human Th1 cells are capable of producing both pro-inflammatory (IL-2, IFN-γ) and anti-inflammatory (IL-10) cytoklnes, therefore the function of these cells may not be accurately encapsulated by the Th1 terminology. We thus investigated the correlation of cytokine production and function in human CD4+ Th1 clones. Cytokine production (IL-2, IFN-γ, IL-10) was measured in supernatants by ELISA after stimulation with solid-phase anti-CD3. The capacity of these supematants to activate or inhibit T cell proliferation or LPS induced TNF-α production by monocytes was assessed. The ratio of IL-2/IL-10 or IFN-y/lL-10 was of critical importance in determining the function of the supematants. 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+ Th1 T cells are heterogeneous in their function, some being pro-inflammatory and others anti-inflammatory. Thus the ‘Th1’ classification with human T cells does not necessarily imply a pro-inflammatory function.

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