Factors contributing to the potency of CD8+ T cells

Trends Immunol. 2023 Sep;44(9):693-700. doi: 10.1016/j.it.2023.07.005. Epub 2023 Aug 7.

Abstract

CD8+ cytotoxic T lymphocytes (CTLs) play a crucial role in targeting virus-infected and cancer cells. Although other cytotoxic lymphocytes such as CD4+ T and natural killer (NK) cells, as well as chimeric antigen receptor (CAR)-T cells, can also identify and destroy aberrant cells, they seem to be significantly less potent based on available experimental data. Here, I contemplate the molecular mechanisms controlling the sensitivity and kinetics of granule-mediated CD8+ T cell cytolytic responses. I posit that the clustering of MHC-I molecules and T cell receptors (TCRs) on the cell surface, as well as the contribution of the CD8 co-receptor, are major factors driving exceptionally potent cytolytic responses. I also contend that CD8+ T cells with known specificity and engineered TCR-T cells might be among the most efficient cytolytic effectors for treating patients suffering from viral infections or cancer.

Keywords: CAR T cells; CD8 and CD4 T cells; CD8 and CD4 co-receptors; TCR and co-receptors clustering; efficiency of cytolytic activity; kinetics of target cell destruction.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • CD8 Antigens
  • CD8-Positive T-Lymphocytes*
  • Humans
  • Killer Cells, Natural
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocytes, Cytotoxic*

Substances

  • Receptors, Antigen, T-Cell
  • CD8 Antigens