Monoclonal antibody to the HLA class I α3 domain inhibits T cell activation and prolongs cardiac allograft survival in HLA- transgenic mice

Jacky Woo, Marie Christine Cornejo, Lan Gao, Joel D Taurog, Robert E Hammer, Roland Buelow

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Antibodies recognizing MHC class I molecules expressed on the surface of T cells have been shown to inhibit T cell responses in vitro. These findings suggested that therapy with such an antibody may prevent rejection and promote graft acceptance. We therefore tested the effect of an anti-HLA class I α3 domain antibody (TP25.99) in vivo using transgenic C57BL/6 mice expressing HLA- B2705. Flow cytometric analysis confirmed the binding of TP25.99 to normal human peripheral blood lymphocytes and to mouse spleen cells, bone marrow cells and thymocytes isolated from hemizygous (+/-) transgenic littermates but not from homozygous (-/-) littermates. TP25.99 inhibited OKT-3-induced, but not PMA+ionomycin-induced, proliferation of human peripheral blood lymphocyte as well as anti-CD3 or Con A-induced proliferation of HLA+ mouse T cells. Both intact monoclonal antibody TP25.99 and TP25.99 Fab inhibited T cell proliferation. Reduced proliferation was associated with suppressed production of interleukin-2 as measured by ELISA. The efficacy of TP25.99 Fab in vivo was evaluated in a heart allograft model. Antibody therapy of (H-2b, B2705+) transgenic recipients of allogeneic Balb/c (H-2(d)) heart grafts prolonged graft survival significantly (MST = 19.8 ± 6.4, p = 0.003) compared to treated (H-2b, B2705-) (MST = 9.17 ± 2.2) or untreated (H-2b, B2705+) (MST = 10.0 ± 2.8) transgenic recipients. This demonstrates that immunomodulation through anti-HLA class I antibody therapy can lead to prolongation of graft survival.

Original languageEnglish (US)
Pages (from-to)112-121
Number of pages10
JournalTransplant Immunology
Volume5
Issue number2
DOIs
StatePublished - Jun 1997

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Transplantation

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