Regulation of C-C Chemokine Production by Murine T Cells by CD28/B7 Costimulation

Kevan C. Herold, Jing Lu, Ingrid Rulifson, Vaiva Vezys, Dennis Taub, Michael J. Grusby, Jeffrey A. Bluestone

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70 Scopus citations


C-C chemokines play an important role in recruitment of T lymphocytes to inflammatory sites. T lymphocytes secrete chemokines, but the activation requirements for chemokine production by T cells are uncertain. We studied the regulation of C-C chemokine production by CD28 costimulatory signals by murine T lymphocytes. Splenocytes from BALB/c mice cultured with anti-CD3 mAb expressed macrophage-inflammatory protein (MIP)-1α mRNA and secreted MIP-1α, which was inhibited by anti-B7-1 plus anti-B7-2 mAbs. MIP-1α production by Ag-stimulated T cells from DO.11.10 TCR transgenic mice was augmented by anti-CD28 mAb and increased compared with DO.11.10/CD28-/- cells. When T cell costimulation was provided by IL-2, MIP-1α was not enhanced. Studies with IL-2, IL-4, STAT4, and STAT6 knock-out mice suggested that chemokine production is controlled by pathways different from those regulating T cell differentiation. Thus, CD28 costimulation may amplify an immune response by stimulating T cell survival, proliferation, and production of chemokines that recruit T cells to inflammatory sites.

Original languageEnglish (US)
Pages (from-to)4150-4153
Number of pages4
JournalJournal of Immunology
Issue number9
StatePublished - Nov 1 1997


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