Selective expansion of memory CD4+ T cells by mitogenic human CD28 generates inflammatory cytokines and regulatory T cells

Manisha Singh, Sreemanti Basu, Christina Camell, Jacob Couturier, Rodolfo J. Nudelman, Miguel A. Medina, John R. Rodgers, Dorothy E. Lewis

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Costimulatory signals are important for development of effector and regulatory T cells. In this case, CD28 signaling is usually considered inert in the absence of signaling through the TCR. By contrast, mitogenic rat CD28 mAb reportedly expand regulatory T cells without TCR stimulation. We found that a commercially available human CD28 mAb (ANC28) stimulated PBMC without TCR co-ligation or cross-linking; ANC28 selectively expanded CD4+CD25+FOXP3- (Teff) and CD4+CD25+FOXP3+ (Treg) cells. ANC28 stimulated the CD45RO+ CD4+ (memory) population, whereas CD45RA+CD4+ (naive) cells did not respond. ANC28 also induced inflammatory cytokines. Treg induced by ANC28 retain the Treg phenotype longer than costimulated Treg. Treg induced by ANC28 suppressed CD25- T cells through a contact-dependent mechanism. Purity influenced the response of CD4+CD25+ cells because bead-purified CD4+CD25+ cells (85-90% pure) responded strongly to ANC28, whereas 98% pure FACS-sorted CD4+CD25bright (Treg) did not respond. Purified CD4+CD25int cells responded similarly to the bead-purified CD4+CD25+ cells. Thus, pre-activated CD4+ T cells (CD25int) respond to ANC28 rather than Treg (CD25bright). The ability of ANC28 to expand both effectors producing inflammatory cytokines aswell as suppressive regulatory T cells might be useful for ex vivo expansion of therapeutic T cells.

Original languageEnglish (US)
Pages (from-to)1522-1532
Number of pages11
JournalEuropean Journal of Immunology
Volume38
Issue number6
DOIs
StatePublished - Jun 2008

Keywords

  • Costimulation
  • Human T cells
  • Inflammation
  • Regulatory T cells
  • T cell activation

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