NKG2D-independent suppression of T cell proliferation by H60 and MICA.
The activating receptor NKG2D recognizes a wide range of different ligands, some of which are primarily expressed in "stressed" tissues or on tumor cells. Until now, similar stimulatory effects on natural killer and CD8+ T cells have been described for all NKG2D ligands, and the NKG2D receptor/ligand system has therefore been interpreted as a sensor system involved in tumor immune surveillance and activation of immune responses. We show here that the NKG2D ligands H60 and MIC class 1 chain-related protein A (MICA) can also mediate strong suppressive effects on T cell proliferation. Responsiveness to H60- and MICA-mediated suppression requires IL-10 and involves a receptor other than NKG2D. These findings might provide explanations for the observation that strong in vivo NKG2D ligand expression, such as that on tumor cells, sometimes fails to support effective immune responses and links this observation to a distinct subgroup of NKG2D ligands.
Kriegeskorte
Anja K
AK
Institute for Medical Microbiology, Immunology, and Hygiene, Technical University Munich, 81675 Munich, Germany.
Gebhardt
Friedemann E
FE
Porcellini
Simona
S
Schiemann
Matthias
M
Stemberger
Christian
C
Franz
Tobias J
TJ
Huster
Katharina M
KM
Carayannopoulos
Leon N
LN
Yokoyama
Wayne M
WM
Colonna
Marco
M
Siccardi
Antonio G
AG
Bauer
Stefan
S
Busch
Dirk H
DH
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens / Q000378:metabolism*; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*
D015395:Histocompatibility Antigens Class I; C527086:Klrk1 protein, mouse; D008024:Ligands; C099187:MHC class I-related chain A; D015778:Minor Histocompatibility Antigens; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; C114735:minor H antigen H60; D016753:Interleukin-10