Expanding role of T-cell costimulators in regulatory T-cell function: recent advances in accessory molecules expressed on both regulatory and nonregulatory T cells

• Published in: Critical reviews in immunology Vol. 24; no. 4; p. 251
• Main Authors: Ndhlovu, Lishomwa C, Takeda, Ikuo, Sugamura, Kazuo, Ishii, Naoto
• Format: Journal Article
• Language: English
• Published: United States 2004
• Subjects: Animals; Antigens, CD - immunology; Antigens, Differentiation, T-Lymphocyte - immunology; CD28 Antigens - immunology; Glycoproteins - immunology; Humans; Immunoglobulins - immunology; Integrins - immunology; Lymphocyte Activation - immunology; Mice; Models, Immunological; Neuropilin-1 - immunology; Receptors, Cell Surface; Receptors, Immunologic - immunology; Receptors, Tumor Necrosis Factor - immunology; Signaling Lymphocytic Activation Molecule Family Member 1; T-Lymphocyte Subsets - immunology; T-Lymphocytes - immunology
• ISSN: 1040-8401
• DOI: 10.1615/CritRevImmunol.v24.i4.30

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 O-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 O-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 O-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.