Anti-CD4 monoclonal antibody-induced tolerance to MHC-incompatible cardiac allografts maintained by CD4+ suppressor T cells that are not dependent upon IL-4.
J Immunol
; 161(10): 5147-56, 1998 Nov 15.
Article
en En
| MEDLINE
| ID: mdl-9820484
ABSTRACT
Anti-CD4 mAb-induced tolerance to transplanted tissues has been proposed as due to down-regulation of Thl cells by preferential induction of Th2 cytokines, especially IL-4. This study examined the role of CD4+ cells and cytokines in tolerance to fully allogeneic PVG strain heterotopic cardiac allografts induced in naive DA rats by treatment with MRC Ox38, a nondepleting anti-CD4 mAb. All grafts survived >100 days but had a minor mononuclear cell infiltrate that increased mRNA for the Thl cytokines IL-2, IFN-gamma, and TNF-beta, but not for Th2 cytokines IL-4 and IL-6 or the cytolytic molecules perforin and granzyme A. These hosts accepted PVG skin grafts but rejected third-party grafts, which were not blocked by anti-IL-4 mAb. Cells from these tolerant hosts proliferated in MLC and produced IL-2, IFN-gamma, and IL-4 at levels equivalent to naive cells. Unfractionated and CD4+ T cells, but not CD8+ T cells, transferred specific tolerance to irradiated heart grafted hosts and inhibited reconstitution of rejection by cotransferred naive cells. This transfer of tolerance was associated with normal induction of IL-2 and delayed induction of IFN-gamma, but not with increased IL-4 or IL-10 mRNA. Transfer of tolerance was also not inhibited by anti-IL-4 mAb. This study demonstrated that tolerance induced by a nondepleting anti-CD4 mAb is maintained by a CD4+ suppressor T cell that is not associated with preferential induction of Th2 cytokines or the need for IL-4; nor is it associated with an inability to induce Th1 cytokines or anergy.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Antígenos CD4
/
Subgrupos de Linfocitos T
/
Trasplante de Corazón
/
Interleucina-4
/
Linfocitos T Reguladores
/
Histocompatibilidad
/
Tolerancia Inmunológica
/
Anticuerpos Monoclonales
Límite:
Animals
Idioma:
En
Revista:
J Immunol
Año:
1998
Tipo del documento:
Article
País de afiliación:
Australia