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.