B and T lymphocyte attenuator regulates CD8+ T cell-intrinsic homeostasis and memory cell generation

Nat Immunol. 2007 Feb;8(2):162-71. doi: 10.1038/ni1418. Epub 2007 Jan 7.


B and T lymphocyte attenuator (BTLA) is a negative regulator of T cell activation, but its function in vivo is not well characterized. Here we show that mice deficient in full-length BTLA or its ligand, herpesvirus entry mediator, had increased number of memory CD8(+) T cells. The memory CD8(+) T cell phenotype resulted from a T cell-intrinsic perturbation of the CD8(+) T cell pool. Naive BTLA-deficient CD8(+) T cells were more efficient than wild-type cells at generating memory in a competitive antigen-specific system. This effect was independent of the initial expansion of the responding antigen-specific T cell population. In addition, BTLA negatively regulated antigen-independent homeostatic expansion of CD4(+) and CD8(+) T cells. These results emphasize two central functions of BTLA in limiting T cell activity in vivo.

Publication types

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

MeSH terms

  • Animals
  • Bone Marrow / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Homeostasis / immunology*
  • Immunologic Memory / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phenotype
  • Receptors, Immunologic / deficiency
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*


  • BTLA protein, mouse
  • Receptors, Immunologic