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 T _R. Furthermore, similar to natural CD4 ⁺CD25 ⁺ T _R, antigen-specific CD8 ⁺CD28 ^-CD62L ⁺ T _S cells have more suppressive capacity than CD8 ⁺CD28 ^-CD62L ^- T _S cells. In spite of these similarities, natural T _R 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.