Research ArticleImmunology

The Inducible Costimulator (ICOS) Is Critical for the Development of Human TH17 Cells

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Science Translational Medicine  27 Oct 2010:
Vol. 2, Issue 55, pp. 55ra78
DOI: 10.1126/scitranslmed.3000448

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Jack of All Trades

Although some immune cells are very specialized, others are thought to do it all. These cells fight infection, contribute to autoimmunity, and engage cancer cells. Paulos et al. explored one such multitasking immune cell type—the T helper 17 (TH17) subset of CD4+ T cells.

T helper cells, which express the molecule CD4, are master regulators of the immune system. Although T helper cells do not directly kill infected cells or produce antibodies to fight bacterial and viral invaders, they are involved in activating and directing the other immune cells that perform these functions. The absence of these cells, as seen in HIV-infected patients, can severely inhibit the immune response.

T helper cells are classified into different subsets based on the molecules they secrete and their subsequent functional responses. The classical paradigm divided these cells into TH1 and TH2 subsets, which activate cellular and humoral immunity, respectively. Further studies indicated that this division was an oversimplification of T helper cell functions, and new T helper cell subsets were identified based on cytokine secretion profiles.

One such T helper cell subset consists of TH17 cells. TH17 cells, which secrete the molecule interleukin-17, are developmentally distinct from TH1 and TH2 cells. TH17 cells are thought to be involved in inflammatory processes, having a pathogenic role in the development of autoimmune disease and a protective role in infection and cancer. Paulos et al. examined cell surface costimulatory molecules, which provide a nonspecific second signal for T cell activation, in the development of TH17 cells. They found that the inducible costimulator (ICOS) was critical for TH17 cell differentiation and that ICOS and not CD28, a costimulatory molecule frequently used to expand TH17 cells, was necessary for the optimal expansion and function of TH17 T cells. Moreover, CD28 stimulation blocked ICOS stimulation, resulting in decreased secretion of TH17-specific cytokines. Indeed, TH17-polarized T cells stimulated with ICOS resulted in higher levels of tumor regression in a mouse xenotransplantation model of mesothelioma than TH17-polarized T cells stimulated with CD28. Therefore, targeting ICOS may provide new therapeutic options for treating cancer and infection as well as inhibiting autoimmunity mediated by TH17 cells, a jack of all trades.


  • Deceased.

  • Citation: C. M. Paulos, C. Carpenito, G. Plesa, M. M. Suhoski, A. Varela-Rohena, T. N. Golovina, R. G. Carroll, J. L. Riley, C. H. June, The inducible costimulator ICOS is critical for the development of human TH17 cells. Sci. Transl. Med. 2, 55ra78 (2010).

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