Potential role of 4-1BB in T cell activation: Comparison with the costimulatory molecule CD28

J. C. Hurtado, S. H. Kim, K. E. Pollok, Z. H. Lee, B. S. Kwon

Research output: Contribution to journalArticle

152 Scopus citations

Abstract

The expression of the murine T cell Ag 4-1BB, a member of the TNF-R family, is induced by T cell activation. Previously, we and others had shown that signaling through 4-1 BB enhanced proliferative T cell responses. To investigate a potential role for the interaction of 4-1 BB with its ligand (4-1BBL) in T cell activation, we studied the ability of a soluble chimera of 4-1 BB (4-1BBFc) to interfere with proliferative responses and cytokine production in models of activation dependent in intercellular interactions. The potential blocking effect of 4-1BBFc was compared with that of the chimeric molecule CTLA-4Ig, a reagent known to interfere with the interaction of CD28 (and/or CTLA-4) with B7 costimulatory receptors. In this study, we report that 4-1BBFc partially blocked both the activation of unfractionated splenocytes triggered by soluble anti-CD3 (anti-CD3s), and the more physiologically relevant responses to alloantigen. In addition, we show that both chimeric molecules partially blocked proliferative responses and IL-2 secretion by highly purified resting T cells activated with anti-CD3s in the presence of fixed accessory cells that express B7 receptors and 4-1BBL. Furthermore, in this model system, the blocking capacity of 4-1BBFc and CTLA-4Ig appears to correlate with the relative expression of their respective cognate receptors (4-1BBL and B7) on the accessory cell. Simultaneous addition of both blocking reagents produced an additive effect in the model systems studied.

Original languageEnglish (US)
Pages (from-to)3360-3367
Number of pages8
JournalJournal of Immunology
Volume155
Issue number7
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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