Direct visualization of cross-reactive effector and memory allo-specific CD8 T cells generated in response to viral infections

J Immunol. 2003 Apr 15;170(8):4077-86. doi: 10.4049/jimmunol.170.8.4077.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / virology
  • Cell Line
  • Cells, Cultured
  • Cytotoxicity Tests, Immunologic* / methods
  • Epitopes, T-Lymphocyte / immunology*
  • Immune Tolerance
  • Immunity, Innate
  • Immunodominant Epitopes / immunology
  • Immunologic Memory*
  • Interferon-gamma / biosynthesis
  • Isoantigens / immunology
  • Lymphocyte Activation / immunology*
  • Lymphocytic Choriomeningitis / immunology
  • Lymphocytic Choriomeningitis / pathology
  • Lymphocytic choriomeningitis virus / immunology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Inbred DBA
  • Mice, Knockout
  • Pichinde virus / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
  • Receptors, Antigen, T-Cell, alpha-beta / physiology
  • Skin Transplantation / immunology
  • Skin Transplantation / pathology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / virology
  • Tumor Cells, Cultured


  • Epitopes, T-Lymphocyte
  • Immunodominant Epitopes
  • Isoantigens
  • Receptors, Antigen, T-Cell, alpha-beta
  • Interferon-gamma