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[Immunosuppressive effect of CTLA-4 blockade and regulatory role of CD8 T cells in Th2-mediated humoral immune responses]
Sakurai J; Second Department of Oral and Maxillofacial Surgery, Faculty
December 30, 2000
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