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One major homeostatic cytokine is IL-7, and studies have linked it or its receptor to the development of multiple sclerosis and other autoimmune diseases. We show in a model of \u03b2-islet cell self-reactivity that the transfer of activated autoreactive CD4 T cells can prime and expand endogenous autoreactive CD8 T cells in a CD28- and CD40-dependent manner through the licensing of dendritic cells. Despite this, mice do not develop diabetes. However, the provision of exogenous IL-7 or the physiological production of IL-7 associated with lymphopenia was able to profoundly promote the expansion of self-reactive clones even in the presence of regulatory T cells. Autoimmune diabetes rapidly ensued with CD4 help and the subsequent activation of CD8 T cells, which contributed to disease progression. With the advent of many biologicals targeting TNF\u03b1, IL-6, and IL-1 and their effective use in the treatment of autoimmune diseases, we propose that IL-7 and its receptor may be promising targets for biological agents in the treatment of autoimmunity.<\/jats:p>","DOI":"10.1073\/pnas.0712135105","type":"journal-article","created":{"date-parts":[[2008,2,15]],"date-time":"2008-02-15T02:13:43Z","timestamp":1203041623000},"page":"2999-3004","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":108,"title":["CD4 T cells, lymphopenia, and IL-7 in a multistep pathway to autoimmunity"],"prefix":"10.1073","volume":"105","author":[{"given":"Thomas","family":"Calzascia","sequence":"first","affiliation":[{"name":"The Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, ON, Canada M5G 2C1"}]},{"given":"Marc","family":"Pellegrini","sequence":"additional","affiliation":[{"name":"The Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, ON, Canada M5G 2C1"}]},{"given":"Albert","family":"Lin","sequence":"additional","affiliation":[{"name":"The Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, ON, Canada M5G 2C1"}]},{"given":"Kristine M.","family":"Garza","sequence":"additional","affiliation":[{"name":"The Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, ON, Canada M5G 2C1"}]},{"given":"Alisha R.","family":"Elford","sequence":"additional","affiliation":[{"name":"The Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, ON, Canada M5G 2C1"}]},{"given":"Arda","family":"Shahinian","sequence":"additional","affiliation":[{"name":"The Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, ON, Canada M5G 2C1"}]},{"given":"Pamela S.","family":"Ohashi","sequence":"additional","affiliation":[{"name":"The Campbell Family 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