Tim R. Mosmann and Subash Sad he T helper 1 (Thl) and Th2 patterns of cytokine production were originally described among mouse CD4’T-cell clone@ and later among human T cells’. Mouse Thl cells produce interleukin 2 (IL-2), interferon y (IFN-y) and lymphotoxin (LT), whereas Th2 cells produce IL-4, IL-5, IL-6, IL-9, IL-10 and IL-13. Human Thl and Th2 cells produce similar patterns, although the synthesis of IL-2, IL-6, IL-10 and IL-13 is not as tightly restricted to a single subset as in mouse T cells. Several other proteins are secreted both by Thl and Th2 cells, including IL-3, tumor necrosis factor a (TNF-o), granulocyte-macrophage colony-stimulating factr r (GM-CSF),[Metlenkephalin and members of the chemokine (CR) families (Table 1). As the full range of cytokines has not been determined in many studies, the terms Thl or Th2 (or type 1 or type 2) will be used here to refer to either the full cytokine patterns defined by mouse T-cell clones, or to responses dominated by IFN-7/or IL-4, respectively. It should be noted that this may underestimate the full complexity of some responses.

The functions of Thl and Th2 cells correlate well with their distinctive cytokines. Thl cells are involved in cell-mediated inflammatory reactions: several Thl cytokines activate cytotoxic and inflammatory functions4; Thl clones induce delayed-type hypersensitivity (DTH) reactions; and IFNy is commonly expressed at sites of DTH reactions5, h. Some B-cell help can be provided by Thl cells but, at higher Thl-cell numbers, this can become suppression7s8. Th2 cytokines encourage antibody production, particularly IgE responses”, and also enhance eosinophil proliferation and function. Accordingly, Th2 cytokines are commoniy found in association with strong antibody and allergic responses. The characteristic cytokine products of Thl and Th2 cells are mutually inhibitory for the differentiation and effector functions of the reciprocal phenotype. Thus, IFN-7 selectively inhibits proliferation of Th2 cells4, and IL-10 inhibits cytokine synthesis by Thl cells9. This cross-regulation may partly explain the strong biases towards Thl or Th2 responses during many infections in mice and humans (Table 2). In severaI cases, alteration of these patterns by cytokine or anti-cytokine reagents reverses host resistance or susceptibility to infection. Thus, there is ample evidence that these cytokine patterns are important in mediating resistance to several infectious agents (reviewed in Ref. 10). C0?).% hi D 19% Elrevlep S< le” ie LLd All rlEhii rereried 0167 W%,%,%, 50”