B7-H1 costimulation preferentially enhances CD28-independent T-helper cellfunction

B7-H1 is a recently described B7-like molecule that costimulates T-cell gro wth and cytokine secretion without binding to CD28, cytotoxic T-lymphocyte antigen-4 (CTLA-4), and inducible costimulator (ICOS), In this report, a mo use homologue of human B7-H1 is identified, and its immunologic functions a re studied in vitro and it: vivo, Mouse B7-H1 shares 69% amino acid homolog y to the human counterpart, Similar to human B7-H1, mouse B7-H1 can be indu ced to express on macrophages, T cells, and B cells and to enhance T-cell p roliferation and secretion of interleukin-10 (IL-10), interferon-gamma, and granulocyte-macrophage colony-stimulating factor but not IL-2 and IL-4, Fu rthermore, B7-H1 preferentially costimulates CD4(+) T cells independently o f CD28 and enhances mixed lymphocyte responses to allogeneic antigens. In c ontrast to B7-1, expression of B7-H1 on murine P815 tumor cells by transfec tion fails to increase allogeneic and syngeneic cytolytic T-cell responses in vitro and in vivo. Administration of B7-H1Ig fusion protein, however, en hances keyhole limpet hemocyanin-specific T-cell proliferation and 2,4,6-tr initrophenyl-specific immunoglobulin G2a antibody production. The study thu s identifies a unique costimulatory pathway that preferentially affects T-h elper cell functions. (Blood, 2001;97:1809-1816) (C) 2001 by The American S ociety of Hematology.