The Janus face of CD4+CD25+ regulatory T cells in cancer and autoimmunity.
Regulatory T cells (Treg) encompass a heterogeneous family of T cells implicated in maintenance of tolerance to self antigens. Treg cells might be qualitatively and/or quantitatively deficient in human autoimmune diseases, including multiple sclerosis, graft versus host disease, systemic lupus erythematosus, type I diabetes, and rheumatoid arthritis. In animal models of autoimmunity, infusion of ex vivo-expanded Treg cells and/or in vivo enhancement of Treg cell suppressor function by pharmacological agents and cytokines attenuate disease manifestations and restore tolerance. However, Treg cells represent a double-edged sword, as Treg cells with specificity for tumour-associated antigens contribute to cancer pathogenesis and progression. In vivo depletion of Treg cells by monoclonal antibodies and/or selected drugs is an encouraging therapeutic strategy which improves tumour eradication in animal models of cancer. In addition, elimination and/or functional inactivation of Treg cells might boost anti-tumour immunity in tumour-bearing hosts receiving anti-cancer vaccination. The present review discusses Treg cell manipulation as a novel therapeutic strategy in cancer and autoimmunity, conditions characterised by a common regulatory basis.
Danese
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S
Department of Hematology, Laboratory of Immunology, Catholic University School of Medicine, Largo A. Gemelli 8, 00168 Rome, Italy.
Rutella
S
S
D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000502:physiology*
D053645:Interleukin-2 Receptor alpha Subunit