CD29 enriches for cytotoxic human CD4+ T cells

Nicolet, Benoît P.; Guislain, Aurelie; Wolkers, Monika C.

CD4+ T cell are key contributors in the induction of adaptive immune responses against pathogens. Even though CD4+ T cells are primarily classified as non-cytotoxic 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. Here, we questioned whether CD29 expression also associates with cytotoxic CD4+ T cells. We show that human peripheral blood-derived CD29hiCD4+ T cells display a cytotoxic gene expression profile, which closely resembles that of CD29hi cytotoxic CD8+ T cells. This CD29hi cytotoxic phenotype was observed ex vivo and was maintained in in vitro cultures. CD29 expression enriched for CD4+ T cells, which effectively produced the pro-inflammatory cytokines IFN-γ, IL-2, and TNF-α, and cytotoxic molecules. Lastly, CD29-expressing CD4+ T cells transduced with a MART-1 specific TCR showed target cell killing in vitro. In conclusion, we here demonstrate that CD29 can be employed to enrich for cytotoxic human CD4+ T cells.