INTRODUCTION
In humans, suppressor activity in peripheral blood mononuclear cells and T cells against differentiation of B cells to immunoglobulin producing plasma cells was described in 1970’s (1,2). Following the discovery of hybridoma and development of monoclonal antibodies, Strelkauskas et al [3] reported natural suppressor activity in OKT8+ (CD8+) T cells, whereas helper activity was in OKT4+ (CD4+) T cells. Damle and Gupta [4, 5] reported generation of suppressor T cells activity in CD8+ T cells following activation with concanavalin A and in autologous T-T mixed lymphocyte reaction. However, the field of suppressor T cells came to a halt due to lack of identification of molecular basis of immune suppression.
In 1982, Damle and Gupta [6] were first to demonstrate that concanavalin A activated CD4+ T cells possess regulatory activity (CD4 Treg), suppressing T cells responses in autologous and allogeneic mixed lymphocyte reaction and response of T cells to pokeweed mitogen. In 1995, Sakaguchi et al (7) further defined regulatory activity of CD4+ T cells in a subset that expressed CD25. However, CD25 was also expressed on non-regulatory CD4+ T cells, especially following activation. In 2003, they reported that FoxP3 transcription factor was responsible for mediating CD4 Treg activity [8]. Since then FoxP3+CD4 Treg have been extensively studies in both mice and human and various diseases and disease models [9, 11].
In past few years there has been renewed interest in CD8+ T regulatory cells. Experiments in mice models of human diseases have provided strong evidence of the presence of CD8+ T regulatory cells (CD8 Treg) and their role in the control of several autoimmune disease models [12-16]. Recently, human CD8+ T cells with suppressor activity have also been implicated in several autoimmune diseases, [17, 18]. Shi and associates [19] have reported that human CD8+CXCR3+ (CD183+) T cells have same function as murine CD8+CD122+ Treg, and suppression of CD8+ T cell function is mediated by IL-10. These cells are CD62L+CD45RA-, similar to central memory CD8+ T cells. We have further characterized FoxP3+ CD8Treg as CD8+CD183+CD25highCD278+(ICOS+). In humans, CD8+ T cell (CD8+CD183+CD62L/CCR7+CD45RA-) regulatory activity has been demonstrated against autologous and allogeneic T cell responses; however, there are no reports of CD8 Treg activity against B cell responses.
Therefore, in this study we have examined the effect of two types CD8 Treg (CD8+CD183+CCR7+CD45RA and CD8+CD183+CD25highCD278+, the later based upon FoxP3 expression), on B cell proliferation and Immunoglobulin production.