T Cell Subsets and In Vitro Immune Regulation in "Infectious" Transplantation Tolerance

CD4-targeted mAb therapy results in permanent acceptance of cardiac allografts in rat recipients, in conjunction with features of the infectious tolerance pathway. Although CD4(+) T cells play a central role, the actual cellular and molecular tolerogenic mechanisms remain elusive. This study was des...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2001-11, Vol.167 (9), p.4814-4820
Main Authors: Zhai, Yuan, Shen, Xiu-Da, Lehmann, Manfred, Busuttil, Ronald, Volk, Hans-Dieter, Kupiec-Weglinski, Jerzy W
Format: Article
Language:English
Subjects:
Animals
CD4 antigen
CD45RC antigen
Heart Transplantation - immunology
Immune Tolerance
Interleukin-2 - pharmacology
Isoantigens - immunology
Leukocyte Common Antigens - physiology
Lymphocyte Activation
Lymphocyte Culture Test, Mixed
Male
Rats
Rats, Inbred BN
Rats, Inbred Lew
Receptors, Interleukin-2 - analysis
T-Lymphocyte Subsets - immunology
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Summary:CD4-targeted mAb therapy results in permanent acceptance of cardiac allografts in rat recipients, in conjunction with features of the infectious tolerance pathway. Although CD4(+) T cells play a central role, the actual cellular and molecular tolerogenic mechanisms remain elusive. This study was designed to analyze in vitro alloimmune responses of T lymphocytes from CD4 mAb-treated engrafted hosts. Spleen, but not lymph node, cells lost proliferative response against donor alloantigen in MLR and suppressed test allograft rejection in adoptive transfer studies, suggesting compartmentalization of tolerogenic T cells in transplant recipients. A high dose of exogenous IL-2 restored the allogeneic response of tolerogenic T cells, indicating anergy as a putative mechanism. Vigorous proliferation of the tolerogenic T cells in in vivo MLR supports the existence of alloreactive lymphocytes in tolerogenic T cell repertoire and implies an active operational suppression mechanism. The tolerogenic splenocytes suppressed proliferation of naive splenocytes in vitro, consistent with their in vivo property of dominant immune regulation. Finally, CD45RC(+) but not CD45RC(-) T cells from tolerant hosts were hyporesponsive to alloantigen and suppressed the proliferation of normal T cells in the coculture assay. Thus, nondeletional, anergy-like regulatory mechanisms may operate via CD4(+)CD45RC(+) T cells in the infectious tolerance pathway in transplant recipients.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.167.9.4814