Mutual regulation between B7-1 (CD80) expressed on T cells and IL-4.
We have used T cells from B7-1-deficient TCR transgenic DO11.10 mice to demonstrate a functional role for B7-1 on T cells. B7-1-deficient DO11.10 T cells produce more IL-4 than wild-type DO11.10 T cells, suggesting that B7-1 expressed by T cells regulates the differentiation of IL-4-producing cells. In addition, we found that IL-4 inhibits B7-1 expression by wild-type DO11.10 T cells. Our results suggest that there is a reciprocal relationship between B7-1 expressed on T cells and IL-4 production, which results in a modulatory feedback loop. When high levels of IL-4 are produced by T cells, B7-1 expression by T cells is inhibited, which allows amplification of IL-4 production by these T cells. When low levels of IL-4 are produced by T cells, B7-1 expression by these T cells is increased, and a further reduction in IL-4 production follows. However, in addition to being influenced by IL-4, B7-1 expression by T cells is affected by peptide concentration and by B7 costimulation from APCs. The studies presented here demonstrate that B7-1 on T cells as well as on APCs regulates IL-4 production. However, whereas B7-1 expression on APCs can promote IL-4 production, IL-4 production is inhibited by B7-1 on T cells.
Schweitzer
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Immunology Research Division, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. nschweitzer@rics.bwh.harvard.edu
Sharpe
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AH
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D018122:B7-1 Antigen / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000502:physiology*; D007399:Interphase / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000276:immunology; D010455:Peptides / Q000276:immunology; D050800:STAT6 Transcription Factor; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics
D018122:B7-1 Antigen; D018984:Epitopes, T-Lymphocyte; D010455:Peptides; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4; D010047:Ovalbumin