CD29 Enriches for Cytotoxic Human CD4+ T Cells

CD4(+) T cells are key contributors in the induction of adaptive immune responses against pathogens. Even though CD4(+) T cells are primarily classified as noncytotoxic helper T cells, it has become appreciated that a subset of CD4(+) T cells is cytotoxic. However, tools to identify these cytotoxic CD4(+) T cells are lacking. We recently showed that CD29 (integrin beta 1, ITGB1) expression on human CD8(+) T cells enriches for the most potent cytotoxic T cells. In this study, we questioned whether CD29 expression also associates with cytotoxic CD4(+) T cells. We show that human peripheral blood -derived CD29(hi)CD4(+) T cells display a cytotoxic gene expression profile, which closely resembles that of CD29(hi) cytotoxic CD8(+) T cells. This CD29(hi) cytotoxic phenotype was observed ex vivo and was maintained in in vitro cultures. CD29 expression enriched for CD4(+) T cells, which effectively produced the proinflammatory cytokines IFN-gamma, IL-2, and TNF-alpha, and cytotoxic molecules. Lastly, CD29-expressing CD4(+) T cells transduced with a MART1-specific TCR showed target cell killing in vitro. In conclusion, we demonstrate in this study that CD29 can be employed to enrich for cytotoxic human CD4(+) T cells.