Cutting edge: p27Kip1 deficiency reduces the requirement for CD28-mediated costimulation in naive CD8+ but not CD4+ T lymphocytes.
Cell cycle re-entry of quiescent T cells is dependent upon cyclin-dependent kinase 2. Inhibition of cyclin-dependent kinase 2 by p27(Kip1) is believed to be the principal constraint on S-phase entry in T cells. We report that deficiency for p27(Kip1) has a more pronounced effect on the expansion of murine naive CD8(+) T cells and that this disparity is due to a reduced requirement for CD28-mediated costimulation in CD8(+) but not CD4(+) T cells lacking p27(Kip1). These data highlight a previously unappreciated difference in the way CD28 signaling is coupled to the core cell cycle machinery in these two T cell subsets.
Wolfraim
Lawrence A
LA
Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. wolfraim@tolergenics.com
Letterio
John J
JJ
D000818:Animals; D018106:CD28 Antigens / Q000235:genetics / Q000502:physiology*; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics*; D049109:Cell Proliferation; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D015536:Down-Regulation / Q000235:genetics* / Q000276:immunology*; D005260:Female; D007700:Kinetics; D008213:Lymphocyte Activation / Q000235:genetics* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*
D018106:CD28 Antigens; C493957:Cdkn1a protein, mouse; C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27