ENHANCED CYTOTOXICITY OF IFN-GAMMA-PRODUCING CD4(-LYMPHOCYTES SPECIFIC FOR T-GONDII-INFECTED HUMAN-MELANOMA CELLS() CYTOTOXIC T)

CD4(+) lines specific for Toxoplasma gondii-infected human melanoma P3 6 cells were established from PBL of a patient with chronic toxoplasmo sis. CD4(+) CTL lines were obtained by weekly in vitro stimulation wit h T. gondii-infected P36 cells that shared HLA-DR4 molecules with the patient. The lytic activity of CD4(+) CTL lines against T. gondii-infe cted P36 or T. gondii-infected autologous EBV-transformed B lymphoma ( EBV-Ya) was inhibited by anti-HLA-DR mAb, whereas anti-HLA-A, B, C mAb failed to block the lytic activity. Thus, the cytotoxicity of CD4(+) CTL lines against T. gondii-infected P36 was restricted by HLA-DR mole cules. In response to Ag-specific stimulation, CD4(+) CTL lines produc ed significant levels of IFN-gamma. Exogenously added IFN-gamma up-reg ulated the surface expression of MHC class II, but not of class I in T . gondii-infected P36 cells. In addition, the CTL activity against T. gondii-infected P36 cells was augmented when target cells were co-cult ured with IFN-gamma. These data indicate that CD4(+) CTL-mediated cyto toxicity against T. gondii-infected melanocytes is enhanced by the aut ocrine production of IFN-gamma. Further, CD4(+) CTL may play a role in the manifestation of toxoplasmic retinochoroiditis by killing T. gond ii-infected melanocytes.