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[Immunosuppressive effect of CTLA-4 blockade and regulatory role of CD8 T cells in Th2-mediated humoral immune responses]




 

Kokubyo Gakkai Zasshi. 2000 Jun;67(2):146-54. Unique Identifier :

CTLA-4 is a negative regulator for T cell activation and plays an important role in down-regulating immune responses and the maintenance of peripheral tolerance. The effect of initial treatment with anti-CTLA-4 mAb on murine acute and chronic graft-versus-host diseases (GVHD) induced by transfer of either C57BL/6 or BALB/c splenocytes into F1 recipient mice has been investigated. The treatment with anti-CTLA-4 mAb exacerbated the lethality of acute GVHD. Surprisingly, in a chronic GVHD model, the similar treatment with anti-CTLA-4 mAb significantly reduced serum IgE and IL-4 expression and ameliorated the manifestation of chronic GVHD. Analysis of the splenic phenotype revealed that blockade of CTLA-4 greatly enhanced donor T cell expansion, especially within the CD8 subset. The transfer of CD8-depleted splenocytes did not exhibit the inhibitory effect by the anti-CTLA-4 mAb treatment, suggesting that CD8 T cells are required for an inhibitory effect of anti-CTLA-4 mAb. The regulatory roles of CD8 T cells and CTLA-4 pathway blockade in Th2-mediated immune responses were further confirmed by in vitro experiments using BALB/c T cell responses to allo-antigen. The immunosuppressive effect of CTLA-4 blockade and the regulatory function of CD8 T cells in Th2-mediated immune responses were demonstrated.

JOURNAL ARTICLE Animal Antibodies, Monoclonal/IMMUNOLOGY/THERAPEUTIC USE Antibody Formation/*IMMUNOLOGY Antigens, Differentiation/*PHARMACOLOGY CD8-Positive T-Lymphocytes/*PHYSIOLOGY English Abstract Female Graft vs Host Disease/IMMUNOLOGY/THERAPY IgE/METABOLISM Immunosuppressive Agents/*PHARMACOLOGY Interferon Type II/METABOLISM Interleukin-4/METABOLISM Mice Mice, Inbred Strains Signal Transduction Th2 Cells/*IMMUNOLOGY



 




Information in this article was accurate in December 30, 2000. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.