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Since the possibility for self\u2010destruction by these cells is high, many regulatory activities exist to prevent autoimmune destruction by these cells. A tumour (cancer) grows from the cells of the body and is tolerated by the body's immune system. Yet, it has been possible to generate tumour\u2010associated antigen (<jats:styled-content style=\"fixed-case\">TAA<\/jats:styled-content>) \u2010specific <jats:styled-content style=\"fixed-case\">CTL<\/jats:styled-content> that are also self\u2010antigen specific <jats:italic>in vivo<\/jats:italic>, to achieve a degree of therapeutic efficacy. Tumour\u2010associated antigen\u2010specific <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\u2010cell tolerance through pathways of self\u2010tolerance generation represents a significant challenge to successful immunotherapy. <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup>\u00a0<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>25<jats:sup>+<\/jats:sup>\u00a0<jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>ox<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>3<jats:sup>+<\/jats:sup> <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content> cells, referred to as <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content> regulatory (<jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>reg) cells, are selected in the thymus as controllers of the anti\u2010self repertoire. These cells are referred to as natural <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content> regulatory (n<jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>reg) cells. According to the new consensus (<jats:italic>Nature Immunology<\/jats:italic> 2013; 14:307\u2013308) these cells are to be termed as (t<jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>reg). There is another class of <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup> Treg cells also involved in regulatory function in the periphery, also phenotypically <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup>\u00a0<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>25<jats:sup>\u00b1<\/jats:sup>, classified as induced <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>reg (i<jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>reg) cells. These cells are to be termed as peripherally induced <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>reg (p<jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>reg) cells. <jats:italic>In vitro<\/jats:italic>\u2010induced Treg cells with suppressor function should be termed as i<jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>reg. These different Treg cells differ in their requirements for activation and in their mode of action. The current challenges are to determine the degree of specificity of these Treg cells in recognizing the same <jats:styled-content style=\"fixed-case\">TAA<\/jats:styled-content> as the <jats:styled-content style=\"fixed-case\">CTL<\/jats:styled-content> population and to circumvent their regulatory constraints so as to achieve robust <jats:styled-content style=\"fixed-case\">CTL<\/jats:styled-content> responses against cancer.<\/jats:p>","DOI":"10.1111\/imm.12387","type":"journal-article","created":{"date-parts":[[2014,9,19]],"date-time":"2014-09-19T16:59:04Z","timestamp":1411145944000},"page":"186-196","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Manipulation of regulatory <scp>T<\/scp> cells and antigen\u2010specific cytotoxic <scp>T<\/scp> lymphocyte\u2010based tumour immunotherapy"],"prefix":"10.1111","volume":"144","author":[{"given":"Shirin","family":"Karimi","sequence":"first","affiliation":[{"name":"Department of Medicine University of Connecticut Health Center Farmington CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Subhasis","family":"Chattopadhyay","sequence":"additional","affiliation":[{"name":"School of Biological Sciences National Institute of Science Education &amp; Research Bhubaneswar Orissa India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nitya G.","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Connecticut Health Center Farmington CT USA"},{"name":"Carole and Ray Neag Comprehensive Cancer Center University of Connecticut Health Center Farmington CT 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