The TNF Superfamily Molecule LIGHT Promotes the Generation of Circulating and Lung-Resident Memory CD8 T Cells following an Acute Respiratory Virus Infection

J Immunol. 2018 Apr 15;200(8):2894-2904. doi: 10.4049/jimmunol.1701499. Epub 2018 Mar 7.

Abstract

The transition of effector T cells or memory precursors into distinct long-lived memory T cell subsets is not well understood. Although many molecules made by APCs can contribute to clonal expansion and effector cell differentiation, it is not clear if clonal contraction and memory development is passive or active. Using respiratory virus infection, we found that CD8 T cells that cannot express the TNF family molecule lymphotoxin-like, exhibits inducible expression, competes with HSV glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes (LIGHT) are unimpaired in their initial response and clonally expand to form effector cell pools. Thereafter, LIGHT-deficient CD8 T cells undergo strikingly enhanced clonal contraction with resultant compromised accumulation of both circulating and tissue-resident memory cells. LIGHT expression at the peak of the effector response regulates the balance of several pro- and antiapoptotic genes, including Akt, and has a preferential impact on the development of the peripheral memory population. These results underscore the importance of LIGHT activity in programming memory CD8 T cell development, and suggest that CD8 effector T cells can dictate their own fate into becoming memory cells by expressing LIGHT.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / immunology
  • Female
  • Immunologic Memory / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Respiratory Tract Infections / immunology*
  • Respiratory Tract Infections / virology
  • Tumor Necrosis Factor Ligand Superfamily Member 14 / immunology*
  • Virus Diseases / immunology*

Substances

  • Tnfsf14 protein, mouse
  • Tumor Necrosis Factor Ligand Superfamily Member 14