Functional analysis of acquired CD28 mutations identified in cutaneous T cell lymphoma

Grzegorz B. Gmyrek, Jeanette Pingel, Jaehyuk Choi*, Jonathan M. Green

*Corresponding author for this work

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

CD28 is the major costimulatory receptor on T cells regulating proliferation, survival and effector function. Acquired mutations in the extracellular domain of CD28 have been identified in patients with cutaneous T cell lymphoma, angioimmunoblastic T cell lymphoma and other T cell neoplasms, suggesting it may contribute to disease pathogenesis. We used a heterologous system in which mutant human CD28 was expressed on primary murine T cells deficient in CD28 to ascertain how specific mutations identified in a genetic screen of patients with cutaneous T cell lymphoma affected normal T cell function. All three mutant CD28 proteins examined enhanced CD28-dependent T cell proliferation and effector function. These data suggest that the mutant CD28 isoforms could accelerate tumor cell growth and increase tumor burden in affected patients. Interruption of CD28:ligand interactions may be an effective, targeted therapy for a subset of patients whose tumors bear the mutant CD28 receptor.

Original languageEnglish (US)
Pages (from-to)28-34
Number of pages7
JournalCellular Immunology
Volume319
DOIs
StatePublished - Sep 1 2017

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Keywords

  • CD28
  • Costimulation
  • Cutaneous T cell lymphoma

ASJC Scopus subject areas

  • Immunology

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