2B4 (CD244) induced by selective CD28 blockade functionally regulates allograft-specific CD8+ T cell responses

Danya Liu, Scott M. Krummey, I. Raul Badell, Maylene Wagener, Lumelle A. Schneeweis, Dawn K. Stetsko, Suzanne J. Suchard, Steven G. Nadler, Mandy L. Ford

Research output: Contribution to journalArticlepeer-review

Abstract

Mounting evidence in models of both autoimmunity and chronic viral infection suggests that the outcome of T cell activation is critically impacted by the constellation of costimulatory and co-inhibitory receptors expressed on the cell surface. Here, we identified a critical role for the co-inhibitory SLAM family member 2B4 (CD244) in attenuating primary antigen-specific CD8+ T cell responses in the presence of immune modulation with selective CD28 blockade. Our results reveal a specific up-regulation of 2B4 on antigenspecific CD8+ T cells in animals in which CD28 signaling was blocked. However, 2B4 upregulation was not observed in animals treated with CTLA-4 Ig (abatacept) or CD28 blockade in the presence of anti-CTLA-4 mAb. 2B4 up-regulation after CD28 blockade was functionally significant, as the inhibitory impact of CD28 blockade was diminished when antigen-specific CD8+ T cells were deficient in 2B4. In contrast, 2B4 deficiency had no effect on CD8+ T cell responses during unmodified rejection or in the presence of CTLA-4 Ig. We conclude that blockade of CD28 signals in the presence of preserved CTLA-4 signals results in the unique up-regulation of 2B4 on primary CD8+ effectors, and that this 2B4 expression plays a critical functional role in controlling antigen-specific CD8+ T cell responses.

Original languageEnglish (US)
Pages (from-to)297-311
Number of pages15
JournalJournal of Experimental Medicine
Volume211
Issue number2
DOIs
StatePublished - Feb 10 2014
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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