Peripheral expression of self-MHC-II influences the reactivity and self-tolerance of mature CD4(+) T cells: evidence from a lymphopenic T cell model

Immunity. 2002 Oct;17(4):425-36. doi: 10.1016/s1074-7613(02)00417-x.


While intrathymic MHC expression influences the specificity of developing thymocytes, we considered that peripheral MHC expression might influence the reactivity of postthymic T cells. We now report for CD4(+) T cells that peripheral MHC-II expression does influence their reactivity and self-tolerance. Upon transfer into MHC-II-deficient lymphopenic hosts, mature CD4(+) T cells were found to acquire an activated memory phenotype and to become: (1) autoreactive against syngeneic MHC-II(+) skin grafts, (2) hyperreactive against third-party MHC-II(+) skin grafts, and (3) functionally dysregulated, resulting in a lymphoproliferative disorder characterized by intraepithelial infiltrations. Peripheral MHC-II expression appeared to influence CD4(+) T cell reactivity by two complementary mechanisms: maintenance of CD4(+)CD25(+) regulatory T cells ("suppression") and direct dampening of CD4(+) T cell reactivity ("tuning").

MeSH terms

  • Adoptive Transfer
  • Animals
  • Autoantigens / metabolism*
  • Autoimmunity
  • CD4-Positive T-Lymphocytes / immunology*
  • Histocompatibility Antigens Class II / metabolism*
  • Immunologic Memory
  • Lymphocyte Activation
  • Lymphopenia / immunology
  • Lymphoproliferative Disorders / etiology
  • Lymphoproliferative Disorders / immunology
  • Lymphoproliferative Disorders / pathology
  • Mice
  • Mice, Knockout
  • Models, Immunological
  • Self Tolerance*
  • Skin Transplantation / immunology
  • Skin Transplantation / pathology
  • T-Lymphocytes / immunology
  • Transplantation, Isogeneic


  • Autoantigens
  • Histocompatibility Antigens Class II