CD28 activation does not down-regulate Cbl-b expression in aged rat T-lymphocytes.
It is well known that T-lymphocyte proliferation declines ex vivo with age, and is associated with decreased expression and/or activity of stimulatory intracellular signaling proteins. However, the role of inhibitory intracellular signaling molecules like the ubiquitin ligase Cbl-b in regulating T-lymphocyte function in aging is largely unknown. Therefore, we tested the hypothesis that T-lymphocyte proliferation declines with age, in part, due to increased expression of Cbl-b. We show that young splenic T-lymphocytes reduced Cbl-b expression when stimulated with anti-CD3 and anti-CD28 antibodies, while in aged T-lymphocytes the CD28-dependent Cbl-b down-regulation did not occur. This effect did not appear to be due to reduced CD28 receptor expression on aged T-lymphocytes. The mechanism for lack of Cbl-b down-regulation may involve the proteasome since blocking proteasomal activity in young T-lymphocytes prevented Cbl-b down regulation while there was no effect in aged T-lymphocytes on Cbl-b expression. These data provide evidence for a novel mechanism by which aging reduces T-lymphocyte function.
Xu
Zhun
Z
Division of Nutritional Sciences, The University of Texas at Austin, 78712, USA.
George
Christy
C
Jolly
Christopher A
CA
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D017252:CD3 Complex / Q000276:immunology; D049109:Cell Proliferation; D015536:Down-Regulation / Q000502:physiology*; D008213:Lymphocyte Activation; D008297:Male; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D050721:Proto-Oncogene Proteins c-cbl; D051381:Rats; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000378:metabolism* / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D000906:Antibodies; D018106:CD28 Antigens; D017252:CD3 Complex; C492213:Cblb protein, rat; D011971:Receptors, Immunologic; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex