Expanding role of T-cell costimulators in regulatory T-cell function: recent advances in accessory molecules expressed on both regulatory and nonregulatory T cells.
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.
Ndhlovu
Lishomwa C
LC
Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
Takeda
Ikuo
I
Sugamura
Kazuo
K
Ishii
Naoto
N
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D016023:Integrins / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018448:Models, Immunological; D039942:Neuropilin-1 / Q000276:immunology; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D000093322:Lymphocyte Activation Gene 3 Protein
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D006023:Glycoproteins; D007136:Immunoglobulins; D016023:Integrins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D018124:Receptors, Tumor Necrosis Factor; C070709:integrin alphaEbeta7; D039942:Neuropilin-1; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D000093322:Lymphocyte Activation Gene 3 Protein