Human TSLP directly enhances expansion of CD8+ T cells

Abstract

Summary 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.