Regulatory T cells and tumor immunity - PubMed (original) (raw)

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Regulatory T cells and tumor immunity

Subhasis Chattopadhyay et al. Cancer Immunol Immunother. 2005 Dec.

Abstract

Central deletion of "self-reactive" T cells has been the textbook paradigm for inducing "self-tolerance" in the periphery and the concept of a role of T cell-mediated suppression in this process has long been controversial. A decisive shift in the opinion on suppressor T cells has lately occurred with the observations of Sakaguchi's group that linked a class of CD4+CD25+ T cells to the prevention of autoimmunity from neonatal thymectomy in mice. These CD4+CD25+ T cells have been named T regulatory (Treg) cells. They are believed to be selected in the thymus as an anti-self repertoire. Hence they were referred to as natural T regulatory (nTreg) cells. Presently, in addition to their role in autoimmunity, they are believed to exert regulatory function in infection, in transplantation immunity as well as in tumor immunity. In contrast to these nTreg cells, another class of CD4+ Treg cells also exercises regulatory function in the periphery. These Treg cells are also CD4+ T cells and after activation they also become phenotypically CD4+CD25+. They are, however induced in the periphery as Treg cells. Hence, they are termed as induced Treg (iTreg) cells. There are major differences in the biology of these two types of Treg cells. They differ in their requirements for activation and in their mode of action. Nonetheless, evidence indicates that both nTreg cells and iTreg cells are involved in the control of tumor immunity. The question of how to circumvent their regulatory constraints, therefore, has become a major challenge for tumor immunologists.

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Fig. 1

Fig. 1

Schematic representation of the operational framework of Treg cell-mediated suppression of antitumor CTL response. The cartoon depicts the basic mechanism underlying the activation of CTLs and the two major types of Treg cells. As shown, while nTregs may not require simultaneous TCR and costimulatory signals to undergo activation and clonal expansion, as do all naive T cells to be functional, we propose that iTregs need to be activated and expanded very much the way all effector T cells also get activated and expanded. iTregs primarily suppress by synthesizing suppressive cytokines while nTregs, after activation, act in a contact-independent mechanism, at least in in vitro experiments, although several groups have shown that nTregs also elaborate immunosuppressive cytokines in vivo (See text). Although we have assembled all three cell types (APC, Treg, and CTL) in the act, we do not imply that the CTL precursors and Tregs need to be activated on the same APC

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