TOXOPLASMA-GONDII POSSESSES A SUPERANTIGEN ACTIVITY THAT SELECTIVELY EXPANDS MURINE T-CELL RECEPTOR V-BETA-5-BEARING CD8+ LYMPHOCYTES

To investigate early immune responses to the intracellular parasite To xoplasma gondii, we examined the capacity of nonimmune splenocytes to respond in vitro to intact tachyzoites and soluble tachyzoite antigen (Ag). Both types of stimuli induced high levels of proliferation as we ll as interferon gamma (IFN-gamma) secretion. Based on several key cri teria, the response appeared to be driven by a superantigen present in the parasite. Thus, stimulation of C57BL/6 spleen cells with T. gondi i resulted in a preferential threefold expansion of a T cell populatio n expressing the V beta 5 chain of the T cell receptor, and a survey o f different inbred mouse strains revealed an inverse correlation betwe en Ag-induced proliferation and genetic deletion of V beta 5. Moreover , proliferation was induced using irradiated Ag-pulsed and infected sp lenic adherent cells, and was blocked by a major histocompatibility co mplex class II-specific monoclonal antibody. Furthermore, paraformalde hyde-fixed IA(b)-, IA(k)-, and IE(k)-transfected fibroblast lines were able to specifically bind T. gondii Ag and drive proliferation of T l ymphocytes, demonstrating that the response can be mediated by allogen eic class II molecules, and that it does not require cellular Ag proce ssing. It is interesting to note that after 1 wk of culture with Ag, u p to 70% of the expanded V beta 5-expressing cells were CD8(+). These results provide the first description of a superantigen activity in a protozoan pathogen. In the case of T. gondii, superantigen-driven expa nsion of IFN-gamma-secreting CD8(+) lymphocytes may play a role in the development of the dominant IFN-gamma - dependent, cell-mediated immu nity characteristic of infection with this parasite.