Differential sensitivity of human T helper cell pathways by in vitro exposure to cyclosporin A

Mario Clerici, Gene M. Shearer

Research output: Contribution to journalArticle

Abstract

Cyclosporin A (CsA) is a widely used agent for the prevention of tissue allograft rejection in human transplantation. As a result of the recent demonstration that the allospecific Th cell response of human PBL can be generated by three distinct pathways of Th cell and APC interactions, we investigated the sensitivity of these three Th-APC pathways, as well as the Th response to recall Ag, to different concentrations of CsA. PBL from healthy volunteer donors were set up as primary in vitro cultures either without antigenic stimulation, or with influenza A virus, tetanus toxoid, or HLA alloantigenic (ALLO) stimulation. Ag-stimulated IL-2 production and proliferation were measured to assess Th cell function. To study the effect of CsA on Th function, different concentrations of CsA (0.001 to 0.1 μg/ml final) were added to the cultures at the time of stimulation. Th responses to influenza A virus and tetanus toxoid were more sensitive to CsA than the Th response to ALLO. By selective depletion of either responder or stimulator APC and/or of CD4+ or CD8+ cells, we 1) verified that the human ALLO Th response can be mediated by three distinct Th-APC pathways; 2) demonstrated that the ALLO response mediated by CD4+ Th and self-APC (the same helper pathway used by recall Ag) is as sensitive to CsA as the responses to recall Ag; and 3) showed that there is a hierarchy of sensitivity of these three allospecific pathways. The results are discussed with respect to the potential significance of the differential sensitivity of these allospecific Th-APC pathways to CsA for prevention of tissue allograft rejection.

Original languageEnglish
Pages (from-to)2480-2485
Number of pages6
JournalJournal of Immunology
Volume144
Issue number7
Publication statusPublished - Apr 1 1990

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Helper-Inducer T-Lymphocytes
Cyclosporine
Tetanus Toxoid
Influenza A virus
Allografts
In Vitro Techniques
Cell Communication
Interleukin-2
Healthy Volunteers
Transplantation
Tissue Donors

ASJC Scopus subject areas

  • Immunology

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Differential sensitivity of human T helper cell pathways by in vitro exposure to cyclosporin A. / Clerici, Mario; Shearer, Gene M.

In: Journal of Immunology, Vol. 144, No. 7, 01.04.1990, p. 2480-2485.

Research output: Contribution to journalArticle

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