NK cells inhibit T cell proliferation via p21-mediated cell cycle arrest.
NK cells have been shown to influence immune responses via direct interaction with cells of the adaptive immune system, such as dendritic cells, B cells, and T cells. A role for NK cells in down-regulation of T cell responses has been implicated in several studies; however, the underlying mechanism of this suppression has remained elusive. In this study we show that dark Agouti rat NK cells inhibit syngeneic T cell proliferation via up-regulation of the cell cycle inhibitor, p21, resulting in a G0/G1 stage cell cycle arrest. The inhibition is cell-cell contact dependent, reversible, and Ag nonspecific. Interestingly, NK cells do not inhibit IL-2 secretion or IL-2R up-regulation and do not induce T cell death. Thus, our results show that NK cells do not affect early T cell activation events, but specifically inhibit T cell proliferation by direct interaction with T cells. Our findings suggest that NK cells may play an important role in maintaining immune homeostasis by directly regulating clonal expansion of activated T cells. This novel mechanism of T cell regulation by NK cells provides insight into NK cell-mediated regulation of adaptive immunity and provides a mechanistic link between NK cell function and suppression of T cell responses.
Trivedi
Prachi P
PP
Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Roberts
Paul C
PC
Wolf
Norbert A
NA
Swanborg
Robert H
RH
D000818:Animals; D002450:Cell Communication; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016193:G1 Phase; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D051381:Rats; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D016192:Resting Phase, Cell Cycle; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation
C493958:Cdkn1a protein, rat; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D007376:Interleukin-2; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D015375:Receptors, Interleukin-2