Overlap between molecular markers expressed by naturally occurring CD4+CD25+ regulatory T cells and antigen specific CD4+CD25+ and CD8+CD28- T suppressor cells

Alloantigen specific CD8(+)CD28(-) T suppressor (T-S) cells differ from naturally occurring CD4(+)CD25(+) T-regulatory (natural T-R) cells not only by their phenotype but also by their mechanism of action. Natural T-R have been extensively studied, leading to the identification of characteristic "molecular markers" such as Forkhead box P3 (FOXP3), glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). We have investigated the expression of these genes in alloantigen specific T-S and CD4(+)CD25(+) T regulatory (T-R) cells and found that they are expressed at levels similar to those observed in natural TR. Furthermore, similar to natural CD4(+)CD25(+) TR, antigen-specific CD8(+)CD28(-)CD62L(+) Ts cells have more suppressive capacity than CD8(+)CD28(-)CD62L(-) Ts cells. In spite of these similarities, natural TR are not antigen-specific and inhibit other T cells by T cell-to-T cell interaction, whereas T-S are antigen-specific and exert their inhibitory function by interacting with antigen-presenting cells and render them tolerogenic to other T cells. The molecular characterization of T-S cells may contribute to a better understanding of mechanisms involved in inhibition of immune responses in autoimmunity, transplantation, and chronic viral infection. (C) American Society for Histocompatibility and Immunogenetics, 2004. Published by Elsevier Inc.