Co-engagement of α4β1 integrin (VLA-4) and CD4 or CD8 is necessary to induce maximal Erk1/2 phosphorylation and cytokine production in human T cells

Tae Kon Kim, Matthew J. Billard, Eric D. Wieder, Bradley W. McIntyre, Krishna V. Komanduri

Research output: Contribution to journalArticle

10 Scopus citations


The α4β1 integrin VLA-4 (very-late activation antigen-4) and the lineage-specific CD4 and CD8 receptors have been proposed as putative co-stimulatory receptors on T cells. To assess the relative contribution of signaling through the TCR, CD28 and these accessory molecules, we activated human T cells using soluble antibodies recognizing all four of these T-cell receptor classes (CD3, CD28, CD4/CD8, and VLA-4), and we assessed the degree of activation using higher-order flow cytometry detecting intracellular Erk1/2 phosphorylation and production of IL-2 and IFN-γ. We found that: (1) co-stimulation via CD4/CD8, in addition to CD28, is required for optimal T-cell activation; (2) VLA-4 binding consistently potentiates CD4+ and CD8+ T-cell activation; (3) augmentation of T-cell activation through VLA-4 binding is most pronounced following engagement of CD4/CD8. These results confirm that multiple signals, including VLA-4 engagement, are necessary for maximal T-cell activation beyond that induced via the TCR and CD28.

Original languageEnglish (US)
Pages (from-to)23-28
Number of pages6
JournalHuman Immunology
Issue number1
StatePublished - Jan 1 2010



  • CD4
  • CD8
  • Co-stimulation
  • Human
  • Integrin
  • T lymphocyte

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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