Enhanced cytotoxicity of IFN-gamma-producing CD4+ cytotoxic T lymphocytes specific for T. gondii-infected human melanoma cells.
CD4+ lines specific for Toxoplasma gondii-infected human melanoma P36 cells were established from PBL of a patient with chronic toxoplasmosis. CD4+ CTL lines were obtained by weekly in vitro stimulation with T. gondii-infected P36 cells that shared HLA-DR4 molecules with the patient. The lytic activity of CD4+ CTL lines against T. gondii-infected 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 molecules. In response to Ag-specific stimulation, CD4+ CTL lines produced significant levels of IFN-gamma. Exogenously added IFN-gamma up-regulated 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-cultured with IFN-gamma. These data indicate that CD4+ CTL-mediated cytotoxicity against T. gondii-infected melanocytes is enhanced by the autocrine production of IFN-gamma. Further, CD4+ CTL may play a role in the manifestation of toxoplasmic retinochoroiditis by killing T. gondii-infected melanocytes.
Yang
T H
TH
Department of Medical Zoology, Nagasaki University School of Medicine, Japan.
Aosai
F
F
Norose
K
K
Ueda
M
M
Yano
A
A
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D015804:HLA-DR4 Antigen / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000378:metabolism; D008545:Melanoma / Q000473:pathology*; D017471:Receptors, Interferon / Q000096:biosynthesis; D011994:Recombinant Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000097:blood / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000469:parasitology; D000096743:Interferon gamma Receptor
D015804:HLA-DR4 Antigen; D007371:Interferon-gamma; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D000096743:Interferon gamma Receptor