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Regulatory T cells and tumor immunity

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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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Abbreviations

Treg:

T regulatory

nTreg:

Natural Tregulatory

iTreg:

Inducible T regulatory

Ts:

T suppressor

APC:

Antigen presenting cell

CTL:

Cytolytic T lymphocytes

MHC:

Major histocompatibility complex

IL:

Interleukin

IFN:

Interferon

TAA:

Tumor associated antigen

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Acknowledgements

The authors thank Robert B Clark for a critical reading of the manuscript and for helpful suggestions. This work was supported by PHS grants CA 88059 and CA83130

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Correspondence to Bijay Mukherji.

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Chattopadhyay, S., Chakraborty, N.G. & Mukherji, B. Regulatory T cells and tumor immunity. Cancer Immunol Immunother 54, 1153–1161 (2005). https://doi.org/10.1007/s00262-005-0699-9

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