| First Author | Śledzińska A | Year | 2020 |
| Journal | Immunity | Volume | 52 |
| Issue | 1 | Pages | 151-166.e6 |
| PubMed ID | 31924474 | Mgi Jnum | J:288600 |
| Mgi Id | MGI:6432042 | Doi | 10.1016/j.immuni.2019.12.007 |
| Citation | Sledzinska A, et al. (2020) Regulatory T Cells Restrain Interleukin-2- and Blimp-1-Dependent Acquisition of Cytotoxic Function by CD4(+) T Cells. Immunity 52(1):151-166.e6 |
| abstractText | In addition to helper and regulatory potential, CD4(+) T cells also acquire cytotoxic activity marked by granzyme B (GzmB) expression and the ability to promote rejection of established tumors. Here, we examined the molecular and cellular mechanisms underpinning the differentiation of cytotoxic CD4(+) T cells following immunotherapy. CD4(+) transfer into lymphodepleted animals or regulatory T (Treg) cell depletion promoted GzmB expression by tumor-infiltrating CD4(+), and this was prevented by interleukin-2 (IL-2) neutralization. Transcriptional analysis revealed a polyfunctional helper and cytotoxic phenotype characterized by the expression of the transcription factors T-bet and Blimp-1. While T-bet ablation restricted interferon-gamma (IFN-gamma) production, loss of Blimp-1 prevented GzmB expression in response to IL-2, suggesting two independent programs required for polyfunctionality of tumor-reactive CD4(+) T cells. Our findings underscore the role of Treg cells, IL-2, and Blimp-1 in controlling the differentiation of cytotoxic CD4(+) T cells and offer a pathway to enhancement of anti-tumor activity through their manipulation. |
