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The control of self\u2010reactive T cells occurs through a process of negative selection that results in apoptosis of T cells showing high affinity for self\u2010peptides expressed at the thymic level by means of promiscuous gene expression. Self\u2010reactive T cells escaped to negative selection are controlled in the periphery by other regulatory mechanisms, the most important being natural Foxp3<jats:sup>+<\/jats:sup> T regulatory (Treg) cells. Regulation is also required to control excessive effector T cell responses against exogenous antigens, when they become dangerous for the body. Three types of effector T cells have been recognized: T helper 1 (Th1) cells, which are protective against intracellular bacteria; Th2 cells, which play some role in the protection against nematodes, but are responsible for allergic reactions; Th17 cells, which are probably effective in the protection against extracellular bacteria, but also play a role in the amplification of autoimmune disorders. Abnormal or excessive Th effector responses are regulated by different mechanisms. Redirection or immune deviation of Th1\u2010 or Th2\u2010dominated responses is provided by cytokines [interferon\u2010\u03b3 (IFN\u2010\u03b3) vs. interleukin\u20104 (IL\u20104)] produced by the same cell types and by the CXCR3\u2010binding chemokines CXCL4 and CXCL10. Moreover, both Th1 and Th2 responses can be suppressed by adaptive Treg cells through contact\u2010dependent mechanisms and\/or the production of IL\u201010 and transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2). Finally, TGF\u2010\u03b21 can promote the development of both Th17 effector and adaptive Treg cells, while the contemporaneous production of IL\u20106 contributes to the development of Th17 cells, but inhibits Treg cells. The development of Th17 cells is also down\u2010regulated by IL\u20104 produced by Th2 cells and by IFN\u2010\u03b3 produced by Th1 cells.<\/jats:p>","DOI":"10.1111\/j.1365-2222.2006.02606.x","type":"journal-article","created":{"date-parts":[[2006,11,2]],"date-time":"2006-11-02T20:14:38Z","timestamp":1162498478000},"page":"1357-1366","source":"Crossref","is-referenced-by-count":294,"title":["Regulation of the T cell response"],"prefix":"10.1111","volume":"36","author":[{"given":"S.","family":"Romagnani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,11,2]]},"reference":[{"key":"e_1_2_5_2_2","volume-title":"Fundamental Immunology","author":"Paul WE.","year":"2003"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2006.01.005"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(01)01889-0"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.21.120601.141107"},{"key":"e_1_2_5_6_2","first-page":"688","article-title":"Self representation in the thymus","volume":"4","author":"Kyewski B","year":"2004","journal-title":"an extended view"},{"key":"e_1_2_5_7_2","first-page":"748","article-title":"AIRE","volume":"16","author":"Su M","year":"2004","journal-title":"an update"},{"key":"e_1_2_5_8_2","first-page":"49","article-title":"Autoimmune polyendocrinopathy syndrome type 1 (APS1) and AIRE gene","volume":"25","author":"Peterson P","year":"2005","journal-title":"new views on molecular basis of autoimmunity"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2006.02.004"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(00)00210-7"},{"key":"e_1_2_5_11_2","first-page":"565","article-title":"CTLA\u20104\u2010mediated inhibition in regulation of T cell responses","volume":"19","author":"Chambers CA","year":"2001","journal-title":"mechanisms and manipulation in tumor immunotherapy"},{"key":"e_1_2_5_12_2","first-page":"1","article-title":"Death receptor signaling and its function in the immune system","volume":"9","author":"Fas SC","year":"2006","journal-title":"Curr Dir Autoimmun"},{"key":"e_1_2_5_13_2","first-page":"124","article-title":"Autoimmune lymphoproliferative syndrome","volume":"133","author":"Worth A","year":"2006","journal-title":"molecular basis of disease and clinical phenotype"},{"key":"e_1_2_5_14_2","doi-asserted-by":"crossref","first-page":"585","DOI":"10.4049\/jimmunol.108.3.586","article-title":"Suppressor T cells","volume":"108","author":"Gershon RK","year":"1972","journal-title":"J Immunol"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.01.040183.002255"},{"key":"e_1_2_5_16_2","first-page":"535","article-title":"Mouse CD1\u2010specific NK1+T cells","volume":"15","author":"Bendelac A","year":"1997","journal-title":"development, specificity, and function"},{"key":"e_1_2_5_17_2","first-page":"1379","article-title":"Going both ways","volume":"114","author":"Godfrey DI","year":"2004","journal-title":"immune regulation via CD1-dependent NKT cells"},{"key":"e_1_2_5_18_2","first-page":"455","article-title":"Regulatory T cells","volume":"101","author":"Sakaguchi S.","year":"2000","journal-title":"key controllers of immunologic self-tolerance"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni904"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/83784"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/83713"},{"key":"e_1_2_5_22_2","first-page":"209","article-title":"Foxp3","volume":"24","author":"Ziegler SF.","year":"2006","journal-title":"of mice and men"},{"key":"e_1_2_5_23_2","first-page":"629","article-title":"CD4+CD25+ regulatory T cells","volume":"112","author":"Holm TD","year":"2004","journal-title":"I. 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