Identification of different functions of CD8+ T cell subpopulations by a novel monoclonal antibody

Abstract

AbstractThe explicit identification of CD8+ T cell subpopulation is important for deciphering the role of CD8+ T cells for protecting our body against invading pathogens and cancer. Our generated monoclonal antibody (mAb), named FE‐1H10, recognized two novel subpopulations of peripheral blood CD8+ T cells, FE‐1H10+ and FE‐1H10− CD8+ T cells. The molecule recognized by mAb FE‐1H10 (FE‐1H10 molecules) had a higher distribution on effector memory CD8+ T cell subsets. The functions of FE‐1H10− and FE‐1H10+ CD8+ T cells were investigated. T cell proliferation assays revealed that FE‐1H10− CD8+ T cells exhibited a higher proliferation rate than FE‐1H10+ CD8+ T cells, whereas FE‐1H10+ CD8+ T cells produced higher levels of IFN‐γ and TNF‐α than FE‐1H10− CD8+ T cells. In T cell cytotoxicity assays, FE‐1H10+ CD8+ T cells were able to kill target cells better than FE‐1H10− CD8+ T cells. RNA‐sequencing analysis confirmed that these subpopulations were distinct: FE‐1H10+ CD8+ T cells have higher expression of genes involved in effector functions (IFNG, TNF, GZMB, PRF1, GNLY, FASL, CX3CR1) while FE‐1H10− CD8+ T cells have greater expression of genes related to memory CD8+ T cell populations (CCR7, SELL, TCF7, CD40LG). The results suggested that mAb FE‐1H10 identifies two novel distinctive CD8+ T cell subpopulations. The FE‐1H10+ CD8+ T cells carried a superior functionality in response to tumour cells. The uncover of these novel CD8+ T cell subpopulations may be the basis knowledge of an optional immunotherapy for the selection of potential CD8+ T cells in cancer treatment.