Human TSLP directly enhances expansion of CD8+ T cells

Clin Exp Immunol. 2008 Oct;154(1):98-106. doi: 10.1111/j.1365-2249.2008.03731.x. Epub 2008 Aug 22.

Abstract

Human thymic stromal lymphopoietin (TSLP) promotes CD4(+) T-cell proliferation both directly and indirectly through dendritic cell (DC) activation. Although human TSLP-activated DCs induce CD8(+) T-cell proliferation, it is not clear whether TSLP acts directly on CD8(+) T cells. In this study, we show that human CD8(+) T cells activated by T-cell receptor stimulation expressed TSLP receptor (TSLPR), and that TSLP directly enhanced proliferation of activated CD8(+) T cells. Although non-stimulated human CD8(+) T cells from peripheral blood did not express TSLPR, CD8(+) T cells activated by anti-CD3 plus anti-CD28 did express TSLPR. After T-cell receptor stimulation, TSLP directly enhanced the expansion of activated CD8(+) T cells. Interestingly, using monocyte-derived DCs pulsed with a cytomegalovirus (CMV)-specific pp65 peptide, we found that although interleukin-2 allowed expansion of both CMV-specific and non-specific CD8(+) T cells, TSLP induced expansion of only CMV-specific CD8(+) T cells. These results suggest that human TSLP directly enhances expansion of CD8(+) T cells and that the direct and indirect action of TSLP on expansion of target antigen-specific CD8(+) T cells may be beneficial to adoptive cell transfer immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology
  • Cell Proliferation
  • Coculture Techniques
  • Cytokines / analysis
  • Cytokines / immunology*
  • Cytomegalovirus / immunology
  • Dendritic Cells / immunology
  • Flow Cytometry
  • Humans
  • Interleukin-2 / immunology
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Lymphocyte Activation / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thymic Stromal Lymphopoietin

Substances

  • Cytokines
  • Interleukin-2
  • Interleukin-2 Receptor alpha Subunit
  • Thymic Stromal Lymphopoietin