The characterization of testicular cell (TC)-specific T-cell clones induced by intratesticular Listeria monocytogenes infection: TC-specific T cells with atypical cytokine profile transfer orchitis.

A unilateral infection of Listeria monocytogenes into the testis of mice induces not only Listeria-specific T cells but also autoreactive T cells that can transfer experimental autoimmune orchitis (EAO) into naive mice. To investigate the characteristics of the autoreactive T cells, we established six testicular cell (TC)-specific T-cell clones from the spleen of the intratesticularly infected mice. All the clones expressed CD4 and T-cell receptor (TCR) alpha beta, and four of the six clones expressed V beta 8. They showed proliferative response to TC in the presence of syngeneic spleen antigen-presenting cells, but did not cross-react to Listeria antigen (Ag). They produced interferon-gamma (IFN-gamma) when stimulated with TC, but interleukin-2 (IL-2), IL-4 and IL-10 were undetectable. IL-2 production was not detected even when they were restimulated with TC after a 10-day resting culture without Ag and IL-2, although they proliferated in the restimulation culture. Even in the presence of anti-IL-2 mAb, the TC-specific T-cell clones showed proliferative response against TC. The observations indicate that the TC-specific IFN-gamma-producing T cells proliferate in the absence of autocrine. Both intravenous and intratesticular injection of these clones transferred EAO in syngeneic naive mice. These results suggest that L. monocytogenes infection in the testis induces autoreactive orchitogenic CD4+ T cells without cross-reactivity to bacterial Ag. Furthermore, these data demonstrate that CD4+ T cells with an atypical cytokine profile can efficiently cause EAO.