The cyclin-dependent kinase inhibitors p27Kip1 and p21Cip1 are not essential in T cell anergy.
Recent evidence suggests that the cyclin-dependent kinase (Cdk) inhibitors p27Kip1 and p21Cip1 are important factors in T cell anergy, but it has remained unclear whether anergy can be induced in their absence. We therefore induced anergy by stimulation of purified T cells from wild-type, p21Cip1-/-, and p27Kip1-/- mice with anti-CD3 antibodies. Anergic wild-type T cells were arrested in the G1 phase of the cell cycle with a high p27Kip1 protein level and low Cdk2 activity. In p27-/- and p21-/- T cells, the pattern of protein expression was preserved, but Cdk2 activity was increased. To confirm the in vivo relevance of these data, anergy was induced by repeated injection of mice with staphylococcal enterotoxin B (SEB), which leads to partial deletion of the responsive Vbeta8+ T cell population and anergy in the remaining T cells. p21-/- mice and wild-type mice reacted similarly to this treatment. p27-/- mice showed reduced deletion of SEB-responsive T cells, but persisting T cells were anergic. These data indicate that other cell cycle regulators contribute to the cell cycle arrest of anergic T cells, as neither Cdk inhibitor is required for the induction of anergy.
Department of Dermatology, University of Erlangen, Erlangen, Germany.
Berlinda
B
Verdoodt
Tino
T
Blazek
Pia
P
Rauch
Gerold
G
Schuler
Alexander
A
Steinkasserer
Manfred B
MB
Lutz
Jens Oliver
JO
Funk
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D017635:Clonal Anergy / Q000276:immunology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D004768:Enterotoxins / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D000942:Antigens, Bacterial; C493957:Cdkn1a protein, mouse; C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004768:Enterotoxins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; C031818:enterotoxin B, staphylococcal; D018844:Cyclin-Dependent Kinases