B and T lymphocyte attenuator regulates CD8+ T cell-intrinsic homeostasis and memory cell generation.
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.
Krieg
Carsten
C
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
Boyman
Onur
O
Fu
Yang-Xin
YX
Kaye
Jonathan
J
D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D006706:Homeostasis / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
C488868:BTLA protein, mouse; D011971:Receptors, Immunologic