Generation and characterization of a continuous line of CD8+ suppressively regulatory T lymphocytes which down-regulates experimental autoimmune orchitis (EAO) in mice

Abstract

SUMMARYWe have previously shown that two injections with viable syngeneic testicular germ cells (TC) alone developed experimental autoimmune orchitis (EAO) in C3H/He mice, and that the induction of antigen-specific tolerance in this EAO model is associated with the generation of antigen-specific suppressively regulatory T (Ts) cells. For the elucidation of the nature of these Ts cells, a murine Ts cell line (designated Ts-A) was established. This line was generated from the spleen cells of C3H/He mice which had received three i.v. injections of a soluble (deaggregated) form of murine testicular antigen (mTA), followed by the repeated selection of these spleen lymphocytes in vitro by stimulation with mTA. Adoptive transfer ofTs-A cells into naive syngeneic mice immediately before the first TC injection was found to downgrade EAO in actively immunized recipients. The transferred Ts-A cells significantly inhibited the cellular immune response to TC in the recipients in an antigen-specific manner, but these cells had no inhibitory effect on the humoral immune response to TC. This line could also inhibit in vitro syngeneic TC-driven proliferation of orchitogenic lymphocytes. Surface phenotype ofthis line was CD8+, CD4-, Thy-i .2+, CD3+, and TCR a,+. These findings may suggest an in vivo role for suppressively regulatory lymphocytes, capable of inhibiting helper T cells, in the regulation of EAO.

CD8+ T Cell-Mediated Suppression of Autoimmunity in a Murine Lupus Model of Peptide-Induced Immune Tolerance Depends on Foxp3 Expression

“…They include CD8 ϩ T cells that are not cytotoxic (2-8), CD4 ϩ CD25 ϩ regulatory T cells that suppress Th cells via cell contact (1, 9 -12), and CD4 ϩ T cells that suppress via secretion of cytokines, including TGF-␤ and IL-10 (13-15). The power of these cells to prevent, delay, or suppress established autoimmunity has been demonstrated in many animal models, including experimental allergic encephalomyelitis (3,14,15), experimental autoimmune orchitis (4), and murine systemic lupus erythematosus (7,8,(11)(12)(13). In the work described in this study, we studied the characteristics of one group of inhibitory T cells (Ti), 3 CD8 ϩ Ti, which we have previously shown are induced in vivo after administration to New Zealand Black/New Zealand White F 1 female (BWF 1 ) mice of a peptide based on amino acid sequences within the V H region of murine Abs to DNA.…”