Viral and bacterial infections induce expression of multiple NK cell receptors in responding CD8(+) T cells.
NK cells express several families of receptors that play central roles in target cell recognition. These NK cell receptors are also expressed by certain memory phenotype CD8(+) T cells, and in some cases are up-regulated in T cells responding to viral infection. To determine how the profile of NK receptor expression changes in murine CD8(+) T cells as they respond to intracellular pathogens, we used class I tetramer reagents to directly examine Ag-specific T cells during lymphocytic choriomeningitis virus and Listeria monocytogenes infections. We found that the majority of pathogen-specific CD8(+) T cells initiated expression of the inhibitory CD94/NKG2A heterodimer, the KLRG1 receptor, and a novel murine NK cell marker (10D7); conversely, very few Ag-specific T cells expressed Ly49 family members. The up-regulation of these receptors was independent of IL-15 and persisted long after clearance of the pathogen. The expression of CD94/NKG2A was rapidly initiated in naive CD8(+) T cells responding to peptide Ags in vitro and on many of the naive T cells that proliferate when transferred into lymphopenic (Rag-1(-/-)) hosts. Thus, CD94/NKG2A expression is a common consequence of CD8(+) T cell activation. Binding of the CD94/NKG2A receptor by its ligand (Qa-1(b)) did not significantly inhibit CD8(+) T cell effector functions. However, expression of CD94 and NKG2A transgenes partially inhibited early events of T cell activation. These subtle effects suggest that CD94/NKG2A-mediated inhibition of T cells may be limited to particular circumstances or may synergize with other receptors that are similarly up-regulated.
Department of Molecular and Cell Biology and Cancer Research Laboratory, University of California, Berkeley, CA 94720, USA.
Christopher W
CW
McMahon
Allan J
AJ
Zajac
Amanda M
AM
Jamieson
Laura
L
Corral
Gianna E
GE
Hammer
Rafi
R
Ahmed
David H
DH
Raulet
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000737:chemistry; D000950:Antigens, Ly; D001424:Bacterial Infections / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D019281:Dimerization; D006706:Homeostasis; D019409:Interleukin-15 / Q000502:physiology; D007694:Killer Cells, Natural / Q000378:metabolism*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000737:chemistry; D055630:Receptors, NK Cell Lectin-Like; D014777:Virus Diseases / Q000276:immunology*
D015703:Antigens, CD; D000950:Antigens, Ly; D019409:Interleukin-15; C497870:Klrd1 protein, mouse; C451496:Klrg1 protein, mouse; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic; D055630:Receptors, NK Cell Lectin-Like