The tumor suppressor p16Ink4a regulates T lymphocyte survival.
In contrast to other cell cycle inhibitors, the tumor suppressor p16Ink4a is not detectable or expressed at very low levels in embryonic and adult mouse tissues, and therefore it has often been considered as a specialized checkpoint protein that does not participate in the control of normal cell cycle progression. However, Ink4a-/- mice possess increased thymus size and cellularity, thus suggesting the involvement of p16(Ink4a) in the control of thymocyte proliferation. In this study, we found increased numbers of CD8 and CD4 T lymphocytes in thymus and spleen from Ink4a-/- mice. Unexpectedly, this was not related to an increase in T-cell division rates, which were similar in lymphoid organs of Ink4a-/- and wild-type mice. In contrast, T-cell apoptosis rates were significantly decreased in thymus and spleen from Ink4a-/- mice. Moreover, whereas p16Ink4a-deficient and wild-type T cells were equally sensitive to Fas or TCR-mediated apoptosis, the former were clearly more resistant to apoptosis induced by oxidative stress or gamma irradiation. Our results indicate that p16Ink4a function is associated with T-cell apoptosis, and subsequently contributes to the control of T-cell population size in lymphoid organs.
Ludwig Institute for Cancer Research, Epalinges, Switzerland.
T
T
Bianchi
N
N
Rufer
H R
HR
MacDonald
M
M
Migliaccio
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology / Q000528:radiation effects; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000235:genetics / Q000276:immunology / Q000528:radiation effects; D002470:Cell Survival / Q000235:genetics / Q000276:immunology / Q000528:radiation effects; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005720:Gamma Rays; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size / Q000276:immunology / Q000528:radiation effects; D018384:Oxidative Stress / Q000235:genetics / Q000276:immunology / Q000528:radiation effects; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology / Q000276:immunology*; D025803:Tumor Suppressor Protein p14ARF / Q000172:deficiency / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology
C417743:Cdkn2a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D011948:Receptors, Antigen, T-Cell; D025803:Tumor Suppressor Protein p14ARF; D019014:fas Receptor