Adjuvant effect of IL-12: conversion of peptide antigen administration from tolerizing to immunizing for CD8+ T cells in vivo.
CD8+ T cells from TCR transgenic 2C mice, specific for SIYRYYGL peptide bound to H-2Kb, were adoptively transferred into C57BL/6 recipients to allow monitoring of their location, numbers, and phenotype upon peptide challenge. Recipients were primed by s.c. injection of SIYRYYGL alone or with CFA or IL-12, and the transferred cells then tracked by flow cytometry using the 1B2 mAb specific for the 2C TCR. Peptide alone induced a transient and weak expansion of 1B2+ cells in the draining lymph nodes (DLN) by day 3, but these cells were tolerant to secondary peptide challenge. In contrast, priming with CFA/peptide resulted in a large clonal expansion of 1B2+ cells in DLN by day 3, and the cells exhibited a CD25highCD44high phenotype, blast transformation, and lytic effector function. By day 5, 1B2+ cell numbers decreased in the DLN and increased in the spleen and blood. 1B2+ cells with a memory phenotype persisted through day 60 in the DLN, spleen, and blood and responded to secondary peptide challenge. Immunization with peptide, along with IL-12, mimicked the adjuvant effects of CFA with respect to phenotype, clonal expansion, effector function, and establishment of memory. IL-12 was not unique in providing this adjuvant effect however, since CFA/peptide immunization of IL-12-deficient recipient mice also resulted in 1B2+ T cell activation and clonal expansion. Thus, CFA or IL-12 can enhance Ag-specific CD8+ T cell responses to peptide, demonstrating that an inflammatory cytokine(s) can support activation and prevent tolerance induction.
Schmidt
C S
CS
Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis 55455, USA.
Mescher
M F
MF
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000502:physiology*; D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D002999:Clone Cells; D005620:Freund's Adjuvant / Q000008:administration & dosage; D007108:Immune Tolerance / Q000187:drug effects; D007114:Immunization; D007156:Immunologic Memory; D018664:Interleukin-12 / Q000494:pharmacology / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009842:Oligopeptides / Q000008:administration & dosage* / Q000276:immunology*; D012995:Solubility; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D000941:Antigens; D009842:Oligopeptides; D018664:Interleukin-12; D005620:Freund's Adjuvant