Activation of CD4+ T lymphocytes form interleukin 2-deficient mice by costimulatory B7 molecules.
Interleukin 2 (IL-2)-deficient (IL-2-/-) mice develop hemolytic anemia and chronic inflammatory bowel disease. Importantly, the induction of disease in IL-2-deficient mice is critically dependent on CD4+ T cells. We have studied the requirements of T cells from IL-2-deficient mice for costimulation with B7 antigens. Stable B7-1 or B7-2 chinese hamster ovary (CHO) cell transfectants could synergize with anti-CD3 monoclonal antibody (mAb) to induce the proliferation of CD4+ T cells from IL-2-/- mutant mice. Further mechanistic studies established that B7-induced activation resulted in surface expression of the alpha chain of the IL-2 receptor. B7-induced proliferation occurred independently of IL-4 and was largely independent of the common gamma chain of the IL-2, IL-4, IL-7, IL-9, and IL-15 receptors. Finally, anti-B7-2 but not anti-B7-1 mAb was able to inhibit the activation of IL-2-/- T cells induced by anti-CD3 mAb in the presence of syngeneic antigen-presenting cells. The results of our experiments indicate that IL-2-/- CD4+ T cells remain responsive to B7 stimulation and raise the possibility that B7 antagonists have a role in the prevention/treatment of inflammatory bowel disease.
Razi-Wolf
Z
Z
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Höllander
G A
GA
Reiser
H
H
D000743:Anemia, Hemolytic / Q000235:genetics / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000276:immunology*; D001483:Base Sequence; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016466:CHO Cells; D006224:Cricetinae; D017931:DNA Primers; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000172:deficiency*; D007700:Kinetics; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology; D014162:Transfection
D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D017252:CD3 Complex; D017931:DNA Primers; D007376:Interleukin-2