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Blood, 15 March 2001, Vol. 97, No. 6, pp. 1809-1816
IMMUNOBIOLOGY
B7-H1 costimulation preferentially enhances
CD28-independent T-helper cell function
Hideto Tamura,
Haidong Dong,
Gefeng Zhu,
Gabriel L. Sica,
Dallas B. Flies,
Koji Tamada, and
Lieping Chen
From the Department of Immunology, Mayo Graduate and
Medical Schools, Mayo Clinic, Rochester, MN.
B7-H1 is a recently described B7-like molecule that costimulates
T-cell growth and cytokine secretion without binding to CD28, cytotoxic
T-lymphocyte antigen-4 (CTLA-4), and inducible costimulator (ICOS). In this report, a mouse homologue of human B7-H1 is
identified, and its immunologic functions are studied in vitro and in
vivo. Mouse B7-H1 shares 69% amino acid homology to the human
counterpart. Similar to human B7-H1, mouse B7-H1 can be induced
to express on macrophages, T cells, and B cells and to enhance
T-cell proliferation and secretion of interleukin-10 (IL-10),
interferon- , and granulocyte-macrophage colony-stimulating factor
but not IL-2 and IL-4. Furthermore, B7-H1 preferentially costimulates
CD4+ T cells independently of CD28 and enhances mixed
lymphocyte responses to allogeneic antigens. In contrast to B7-1,
expression of B7-H1 on murine P815 tumor cells by transfection fails to
increase allogeneic and syngeneic cytolytic T-cell responses in
vitro and in vivo. Administration of B7-H1Ig fusion protein,
however, enhances keyhole limpet hemocyanin- specific T-cell
proliferation and 2,4,6-trinitrophenyl-specific immunoglobulin
G2a antibody production. The study thus identifies a unique
costimulatory pathway that preferentially affects T-helper cell functions.
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