Heart allografts in murine systems. The differential activation of Th2-like effector cells in peripheral tolerance

Transplantation. 1992 Jun;53(6):1281-94.


Activated CD4+ Th2 cells release cytokines (IL-4,-10) that block activation & cytokine (IL-2/IFN-gamma) release by proinflammatory T (CD4+,CD8+) effector cells. To test the hypothesis that peripheral tolerance to alloantigen is linked to differential activation of CD4+ Th2 cells we measured cytokine transcripts in heart grafts (C57BL/10----C3H/HeJ) and spleens of mice rendered "tolerant" by donor-specific blood transfusion, anti-CD4 mAb pretreatment, and cyclosporine administration. The expression of IL-2/IFN-gamma transcripts was reduced greater than 90% in grafts from tolerant recipients. IL-4/IL-10 transcripts were generally enhanced and persisted in graft and recipient spleen. Accordingly adoptive transfer studies were performed to determine whether Th2-like effectors, which express Fc receptors (FcR), mediate suppression in this model. Unfractionated mononuclear cells (MC) (5 x 10(6), isolated from spleens of heart graft recipients made tolerant by DST, prolonged the survival of test grafts greater than 90 days in irradiated (680 rads) recipients reconstituted with a sufficient number of MC from spleens of naive C3H to precipitate rejection of the test graft in 18.2 days (MST, n = 5). Conversely adoptive transfer of inocula depleted of FcR+ cells on immune complex columns or with anti-FcR mAb 24G2 caused test grafts to be rejected in 8-11 days. These results suggest that peripheral tolerance to alloantigen may be linked to differential activation of Th2 cells that induce anergy by suppression. The possibility that Th2-like effectors mediate peripheral tolerance to self is discussed.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • B-Lymphocytes / immunology*
  • CD4 Antigens / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • Cyclosporine / administration & dosage
  • Cytokines / physiology
  • Heart Transplantation / immunology*
  • Hypersensitivity, Delayed / immunology
  • Immune Tolerance
  • Immunotherapy, Adoptive
  • Interferon-gamma / pharmacology
  • Interleukin-10 / analysis
  • Interleukin-2 / analysis
  • Interleukin-4 / analysis
  • Male
  • Mice
  • Polymerase Chain Reaction
  • Receptors, Fc / analysis
  • Spleen / chemistry
  • Spleen / physiology
  • T-Lymphocytes, Helper-Inducer / ultrastructure
  • Transplantation, Homologous / physiology


  • Antibodies, Monoclonal
  • CD4 Antigens
  • Cytokines
  • Interleukin-2
  • Receptors, Fc
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma
  • Cyclosporine