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In the present study, we have identified a third population of memory CD4 T\u2004cells characterized as CD45RA<jats:sup>+<\/jats:sup>CCR7<jats:sup>\u2013<\/jats:sup> that, based on its replication history and the homeostatic proliferative capacity, was at an advanced stage of differentiation. Three different phenotypic patterns of memory CD4 T\u2004cell responses were delineated under different conditions of antigen (Ag) persistence and load using CD45RA and CCR7 as markers of memory T\u2004cells. Mono\u2010phenotypic CD45RA<jats:sup>\u2013<\/jats:sup>CCR7<jats:sup>+<\/jats:sup> or CD45RA<jats:sup>\u2013<\/jats:sup>CCR7<jats:sup>\u2013<\/jats:sup> CD4 T\u2004cell responses were associated with conditions of Ag clearance (tetanus toxoid\u2010specific CD4 T\u2004cell response) or Ag persistence and high load (chronic HIV\u20101 and primary CMV infections), respectively. Multi\u2010phenotypic CD45RA<jats:sup>\u2013<\/jats:sup>CCR7<jats:sup>+<\/jats:sup>, CD45RA<jats:sup>\u2013<\/jats:sup>CCR7<jats:sup>\u2013<\/jats:sup> and CD45RA<jats:sup>+<\/jats:sup>CCR7<jats:sup>\u2013<\/jats:sup> CD4 T\u2004cell responses were associated with protracted Ag exposure and low load (chronic CMV, EBV and HSV infections and HIV\u20101 infection in long\u2010term nonprogressors). The mono\u2010phenotypic CD45RA<jats:sup>\u2013<\/jats:sup>CCR7<jats:sup>+<\/jats:sup> response was typical of central memory (T<jats:sub>CM<\/jats:sub>) IL\u20102\u2010secreting CD4 T\u2004cells, the mono\u2010phenotypic CD45RA<jats:sup>\u2013<\/jats:sup>CCR7<jats:sup>\u2013<\/jats:sup> response of effector memory (T<jats:sub>EM<\/jats:sub>) IFN\u2010\u03b3\u2010secreting CD4 T\u2004cells and the multi\u2010phenotypic response of both IL\u20102\u2010 and IFN\u2010\u03b3\u2010secreting cells. The present results indicate that the heterogeneity of different Ag\u2010specific CD4 T\u2004cell responses is regulated by Ag exposure and Ag load.<\/jats:p>","DOI":"10.1002\/eji.200425324","type":"journal-article","created":{"date-parts":[[2004,10,14]],"date-time":"2004-10-14T12:05:00Z","timestamp":1097755500000},"page":"3525-3533","source":"Crossref","is-referenced-by-count":159,"title":["Phenotypic heterogeneity of antigen\u2010specific CD4 T cells under different conditions of antigen persistence and antigen load"],"prefix":"10.1002","volume":"34","author":[{"given":"Alexandre","family":"Harari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Vallelian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Pantaleo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,11,26]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.20.100101.151926"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.18.1.561"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni969"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5258.54"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri778"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/87720"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5489.92"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri959"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.9.1407"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/11.7.1027"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(02)02326-8"},{"key":"e_1_2_7_12_2","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.4049\/jimmunol.154.3.1408","article-title":"Th0\/Th2\u2010like function of CD4+CD7\u2013 T helper cells from normal donors and HIV\u2010infected patients.","volume":"154","author":"Autran B.","year":"1995","journal-title":"J. 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