Altered effector responses of H-Y transgenic CD8+ cells.
The primary role of CD8+ T cells is to destroy virus-infected or tumor cells expressing cognate antigens in the form of peptide-MHC class I complexes. This destruction is primarily achieved by the actions of lytic mediators and/or lymphokines. In this report, we show that mature, H-Y/Db-specific CD8+ T cells from H-Y TCR transgenic mice were unable to efficiently release lytic mediators after antigenic stimulation. However, anti-TCR antibody induced granule exocytosis and target cell lysis, arguing against signaling and/or cytolytic machinery defects in CD8+ cells, and demonstrating that male antigen induced differentiation of 'naive' into effector CD8+ cells. Stimulation of H-Y-specific effector CD8+ T cells with male stimulators, although insufficient to induce lytic granule release, was sufficient for H-Y-specific IFN-gamma production. Unexpectedly, this effector-phase IFN-gamma production was dependent on B7-2 engagement. We hypothesize that altered effector functions in H-Y-specific CD8+ cells are due to the low affinity of TCR-antigen-MHC interaction and/or the elevated threshold of CD8+ T cell activation.
Arsov
I
I
Michael Heidelberger Division of Immunology, Department of Pathology, NYU Medical Center, NY 10016, USA.
Vukmanović
S
S
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D004950:Esterases / Q000378:metabolism; D005260:Female; D006182:H-Y Antigen / Q000235:genetics*; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D008822:Mice, Transgenic; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism
D006182:H-Y Antigen; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D054353:Perforin; D007371:Interferon-gamma; D004950:Esterases; C022635:serine esterase