CD40L expressing helper CD8+ T cells in human skin

• Applicant: Dr. Lucie Loyal
• Subject Area: Immunology ; Clinical Immunology and Allergology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 542630205

TCR α/β T cells are commonly subclassified into MHC-class-II-restricted, CD40L expressing helper CD4+ T cells responsible for B cell maturation and APC licensing and MHC-class-I-restricted cytotoxic CD8+ T cells that directly kill infected cells. However, cytotoxic CD4+ T cells as well as helper CD8+ T cells lacking cytotoxic features and expressing CD40L have been described in particular in the human immune system. In prework we demonstrated that memory CD8+ T cell possess a CD4+ alike diversity and that they can be subclassified into Tc1, Tc2, Tc17, Tc17+1 and Tc22 cells based on their chemokine receptor expression, cytokine secretion and gene expression. Among them, Tc2, Tc17 and Tc22 CD8+ helper cells lacked the ability to kill and expressed a unique TCR repertoire different from the cytotoxic Tc1 and Tc17+1 cell subsets. These CD40L expressing helper CD8+ T cells also displayed a skin migratory phenotype and were enriched in the blood of psoriasis patients. However, the exact role of CD8+ helper T cells in steady state health conditions and in human inflammatory disorders has remained unclear so far, also because of a lack of adequate experimental models. In this proposal we aim to elucidate the mechanisms of induction of human CD8+ helper T cells and their contribution to maintain skin homeostasis and inflammation.

• DFG Programme: Research Grants