Mcl-1 regulates effector and memory CD8 T-cell differentiation during acute viral infection

Virology. 2016 Mar:490:75-82. doi: 10.1016/j.virol.2016.01.008. Epub 2016 Feb 6.

Abstract

Mcl-1, an anti-apoptotic member of Bcl-2 family maintains cell viability during clonal expansion of CD8 T cells, but the cell intrinsic role of Mcl-1 in contraction of effectors or the number of memory CD8 T cells is unknown. Mcl-1 levels decline during the contraction phase but rebound to high levels in memory CD8 T cells. Therefore, by overexpressing Mcl-1 in CD8 T cells we asked whether limiting levels of Mcl-1 promote contraction of effectors and constrain CD8 T-cell memory. Mcl-1 overexpression failed to affect CD8 T-cell expansion, contraction or the magnitude of CD8 T-cell memory. Strikingly, high Mcl-1 levels enhanced mTOR phosphorylation and augmented the differentiation of terminal effector cells and effector memory CD8 T cells to the detriment of poly-cytokine-producing central memory CD8 T cells. Taken together, these findings provided unexpected insights into the role of Mcl-1 in the differentiation of effector and memory CD8 T cells.

Keywords: Apoptosis; Central memory; Differentiation; Effector; Effector memory; Lymphocytic choriomeningitis virus; Mammalian target of rapamycin; Memory; Myeloid cell leukemia 1.

Publication types

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

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation*
  • Humans
  • Immunologic Memory*
  • Lymphocytic Choriomeningitis / genetics
  • Lymphocytic Choriomeningitis / immunology*
  • Lymphocytic Choriomeningitis / physiopathology
  • Lymphocytic Choriomeningitis / virology
  • Lymphocytic choriomeningitis virus / immunology
  • Lymphocytic choriomeningitis virus / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Myeloid Cell Leukemia Sequence 1 Protein / genetics
  • Myeloid Cell Leukemia Sequence 1 Protein / immunology*
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / immunology

Substances

  • Mcl1 protein, mouse
  • Myeloid Cell Leukemia Sequence 1 Protein
  • TOR Serine-Threonine Kinases