Direct visualization of cross-reactive effector and memory allo-specific CD8 T cells generated in response to viral infections.
CD8 T cell cross-reactivity between heterologous viruses has been shown to provide protective immunity, induce immunopathology, influence the immunodominance of epitope-specific T cell responses, and shape the overall memory population. Virus infections also induce cross-reactive allo-specific CTL responses. In this study, we quantified the allo-specific CD8 T cells elicited by infection of C57BL/6 (B6) mice with lymphocytic choriomeningitis virus (LCMV). Cross-reactive LCMV-specific CD8 T cells were directly visualized using LCMV peptide-charged MHC tetramers to costain T cells that were stimulated to produce intracellular IFN-gamma in response to allogeneic target cells. The cross-reactivity between T cells specific for LCMV and allogeneic Ags was broad-based, in that it involved multiple LCMV-derived peptides, but there were distinctive patterns of reactivity against allogeneic cells with different haplotypes. Experiments indicated that this cross-reactivity was not due to the expression of two TCR per cell, and that the patterns of allo-reactivity changed during sequential infection with heterologous viruses. The allo-specific CD8 T cells generated by LCMV infection were maintained at relatively high frequencies in the memory pool, indicating that memory allo-specific CD8 T cell populations can arise as a consequence of viral infections. Mice previously infected with LCMV and harboring allo-specific memory T cells were refractory to the induction of tolerance to allogeneic skin grafts.
Brehm
Michael A
MA
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Markees
Thomas G
TG
Daniels
Keith A
KA
Greiner
Dale L
DL
Rossini
Aldo A
AA
Welsh
Raymond M
RM
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D007108:Immune Tolerance; D007113:Immunity, Innate; D016056:Immunodominant Epitopes / Q000276:immunology; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000473:pathology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D018052:Pichinde virus / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000502:physiology; D016038:Skin Transplantation / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D014407:Tumor Cells, Cultured
D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D007519:Isoantigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma