Regulatory T cells essential to prevent the loss of self-tolerance in murine models of erythrocyte-specific autoantibody responses

Abstract

The spontaneous appearance of anti-erythrocyte autoantibodies resulting in autoimmune hemolytic anemia described in NZB mice more than 40 years ago provided a model for the study of mechanisms behind the loss of self-tolerance. We developed an in vitro model of this anti-MRBC response in which CD8(+) suppressor T cells were shown to be a controlling element. CD8(+) T cells from young NZB mice co-cultured with spleen cells from old, actively autoimmune NZB mice suppressed the anti-MRBC responses of the old mice. Eliminating the CD8(+) cells from young NZB spleen cells or even from non-autoimmune BALB/c spleen cells prior to culture removed the controlling influence of these CD8(+) cells and allowed the development of anti-MRBC-secreting cells. This review will consider the role of the CD8(+) suppressive cells in the anti-self-erythrocyte model in light of insights provided by current 'regulatory T cell' literature.

Indoleamine 2,3 dioxygenase contributes to transferable tolerance in rat red blood cell inducible model of experimental autoimmune haemolytic anaemia

“…+ T cells from young NZB mice were co-cultured with splenic cells from old, actively autoimmune NZB mice indicated that these CD8 + T cells were capable of suppressing autoantibody responses, evidence that they may also have a role in regulating disease [11]. While identification of the T cell subset(s) that mediate and transmit tolerogenic responses in AIHA continues, it is also important to address, at a molecular level, mechanisms that underpin this important immunological feature.…”

“…In this model system, the mechanism by which splenic lymphocytes 'transfer' tolerance to the recipients remains unknown, although a role for CD4 + CD25 + regulatory T cells has been suggested [10]. Further, analysis of in-vitro assays where CD8 + T cells from young NZB mice were co-cultured with splenic cells from old, actively autoimmune NZB mice indicated that these CD8 + T cells were capable of suppressing autoantibody responses, evidence that they may also have a role in regulating disease [11]. While identification of the T cell subset(s) that mediate and transmit tolerogenic responses in AIHA continues, it is also important to address, at a molecular level, mechanisms that underpin this important immunological feature.…”