| First Author | Kovalev GI | Year | 2001 |
| Journal | J Immunol | Volume | 167 |
| Issue | 6 | Pages | 3285-92 |
| PubMed ID | 11544316 | Mgi Jnum | J:118562 |
| Mgi Id | MGI:3699775 | Doi | 10.4049/jimmunol.167.6.3285 |
| Citation | Kovalev GI, et al. (2001) An important role of CDK inhibitor p18(INK4c) in modulating antigen receptor-mediated T cell proliferation. J Immunol 167(6):3285-92 |
| abstractText | The inhibitors of cyclin-dependent kinase (CDK) 4 (INK4) bind CDK4/6 to prevent their association with D-cyclins and G(1) cell cycle initiation and progression. We report here that among the seven CDK inhibitors, p18(INK4c) played an important role in modulating TCR-mediated T cell proliferation. Loss of p18(INK4c) in T cells led to hyperproliferation in response to CD3 stimulation. p18(INK4c)-null mice developed lymphoproliferative disorder and T cell lymphomas. Expression of IL-2, IL-2R-alpha, and the major G(1) cell cycle regulatory proteins was not altered in p18-null T cells. Both FK506 and rapamycin efficiently inhibited proliferation of p18-null T cells. In activated T cells, p18(INK4c) remained constant, and preferentially associated with and inhibited CDK6 but not CDK4. We propose that p18(INK4c) sets an inhibitory threshold in T cells and one function of CD28 costimulation is to counteract the p18(INK4c) inhibitory activity on CDK6-cyclin D complexes. The p18(INK4c) protein may provide a novel target to modulate T cell immunity. |
