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Critical Reviews™ in Immunology

ISSN for PRINT: 1040-8401

Institutional price:	$831.00
Issues per year:	6

Best Paper Award Selection - Editorial Board Site

2004, Volume24

69 pages

DOI: 10.1615/CritRevImmunol.v24.i4

Issue price - $132.00

Expanding Role of T-Cell Costimulators in Regulatory T-Cell Function: Recent Advances in Accessory Molecules Expressed on Both Regulatory and Nonregulatory T Cells

Lishomwa C. Ndhlovu
Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan

Ikuo Takeda
Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan

Kazuo Sugamura
Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan

Naoto Ishii
Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan

ABSTRACT

A subpopulation of T cells harbors a suppressor phenotype and can significantly dampen autoreactive CD4⁺ and CD8⁺ T-cell responses. These regulatory T (Treg) cells, which can arise naturally in the thymus and encompass a CD25⁺CD4⁺ T-cell repertoire or be antigenically induced, are central players in the maintenance of self-tolerance. A plethora of T-cell costimulatory and accessory receptor molecules expressed by Treg and/or non-regulatory T cells, such as GITR, OX40, and CTLA-4, are involved in modulating the pathogenesis of numerous autoimmune disorders, transplant rejection, and tumor immunity, as well as the control of infections. Exciting new evidence shows that T-cell costimulators, some of which are identified as hopeful discriminative Treg-cell markers, appear to mediate Treg-cell homeostasis and function. Understanding the biological significance of the T-cell costimulatory molecules and the accessory molecules expressed by Treg cells is a prerequisite to better characterizing this regulatory T-cell population. We provide a synopsis of the current understanding of several costimulatory molecules that can orchestrate the function of both naturally arising and antigen-inducible Treg cells.