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Human anti-porcine T cell response: blocking with anti-class I antibody leads to hyporesponsiveness and a switch in cytokine production.
DerSimonian H; Pan L; Yatko C; Rodrigue-Way A; Johnson E; Edge AS;
September 30, 1999
J Immunol. 1999 Jun 15;162(12):6993-7001. Unique Identifier : AIDSLINE

Intervention in the molecular interactions that lead to an immune response is possible at various stages of Ag recognition and T cell activation. Perturbation of the interaction of the TCR with the MHC/peptide ligand complex is one approach that has shown promise for autoimmunity and graft rejection in blocking T cell-activated responses. In this study, we investigated the effect of altering the target MHC class I molecule by blocking with Abs. We established a system that analyzed the human T cell response against MHC class I+/class II- porcine stimulatory cell targets. The primary human response against porcine smooth muscle cells was CD8+ T cell dependent. In the presence of F(ab')2 fragments of the MHC class I-reactive Ab, PT-85, the proliferative response was inhibited and production of IL-2 and IFN-gamma was blocked. Moreover, in a secondary response, proliferation was reduced and type 1 cytokine levels were inhibited. In contrast, levels of IL-10 and IL-4 were sustained or slightly increased. These findings indicate that Ab against MHC class I blocked the recognition of porcine cells by the human CD8+ T cells and altered the cytokine secretion profile. Thus, a single treatment with PT-85 F(ab')2 directed against the MHC class I molecule provides an attractive approach to the induction of T cell tolerance that may provide long-term graft survival in porcine-to-human cell transplantation.

JOURNAL ARTICLE Animal Antibodies/CHEMISTRY/METABOLISM/*PHARMACOLOGY Antibodies, Blocking/CHEMISTRY/METABOLISM/PHARMACOLOGY Antibody Specificity Antigens, CD8/IMMUNOLOGY Cells, Cultured Cytokines/*BIOSYNTHESIS CD8-Positive T-Lymphocytes/IMMUNOLOGY Histocompatibility Antigens Class I/*IMMUNOLOGY/METABOLISM Human Immune Tolerance/*IMMUNOLOGY Immunoglobulins, Fab/PHARMACOLOGY Interferon Type II/ANTAGONISTS & INHIB Interleukin-10/BIOSYNTHESIS Interleukin-2/ANTAGONISTS & INHIB Interleukin-4/BIOSYNTHESIS Leukocytes, Mononuclear/IMMUNOLOGY Mice Mice, Inbred BALB C Swine/*IMMUNOLOGY Swine, Miniature T-Lymphocytes/*IMMUNOLOGY

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