Induction of antigen-specific tolerance in vivo by blockade of T cell costimulation

D. I. Daikh, D. Wofsy

Research output: Contribution to journalArticlepeer-review

Abstract

T cell costimulation can be provided by the interaction between CD28 on T cells and B7 molecules on APC, or between gp39 (CD40L) on T cells and CD40 on APC. In vitro studies suggest that interruption of these costimulatory pathways individually can lead to antigen-specific unresponsiveness. However, attempts to translate the in vitro observations into in vivo systems have met with mixed results. To test the hypothesis that combined interruption of both the B7/CD28 and the gp39/CD40 costimulatory pathways might induce antigen-specific tolerance in vivo, we administered KLH to BALB/c females (100 μg ip/week for 4 weeks) during treatment with anti-gp39 (250 μg ip), CTLA4Ig (50 μg ip), both anti-gp39 and CTLA4Ig, or control antibodies thrice weekly for two weeks. The mice were rested for 5 weeks and then rechallenged with KLH (100 μg ip/week for 4 weeks) without further immunosuppressive therapy. Mice receiving anti-gp39 or CTLA4Ig exibited diminished anti-KLH responses during treatment compared with controls, but subsequently developed a response upon rechallenge. In contrast, mice treated with both anti-gp-39 and CTLA4Ig exibited no response to the antigen even upon rechallenge. These mice were capable of responding normally to other antigens. These findings indicate that blockade of either pathway alone suppresses primary immune responses but does not induce antigen-specific tolerance. In contrast, combined blockade of the CD28/B7 and gp39/CD40 costimulatory pathways can induce long-lasting antigen-specific tolerance in normal mice.

Original languageEnglish (US)
Pages (from-to)A933
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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