Induction and tolerization of anti-male CD8(+) cytotoxic T lymphocytes by in vivo immunization with an H-Y-derived peptide

We have analyzed the immune response induced by a 9mer synthetic peptide de rived from the male histocompatibility antigen H-Y and containing D-b-bindi ng motifs in C57BL/6 mice. In this study we report that a single, subcutaneous injection of the peptid e emulsified in IFA Save rise to the development of male-specific CD8(+) T cells which displayed H-Y-specific proliferative response in vitro and show ed a Tcl-type pattern of cytokine production (i.e. they secreted IFN-gamma and IL-2, but not. IL-4 and IL-10). Development of a strong cytotoxic activ ity required in vitro stimulation with specific peptide and IL-2: under the se culture conditions, we were able to generate potent CD8(+) CTLs that lys ed both male cells and peptide-pulsed female cells. Continuous administration of soluble peptide, delivered over a 7-day period by a mini-osmotic pump implanted subcutaneously, inhibited proliferative a nd cytotoxic responses and IFN-gamma production in lymph node cells from C5 7BL/6 mice subsequently primed with peptide in adjuvant. This decreased res ponses were associated with a strong increase in the secretion of IL-4 by a ntigen-specific CD8(+) T lymphocytes, Subcutaneous administration of the H-Y-peptide in adjuvant significantly ac celerates rejection of male skin graft, while continuous administration of peptide in soluble form did not modify the time course of rejection. (C) Am erican Society for Histocompatibility and Immunogenetics, 1999. Published b y Elsevier Science Inc.