| First Author | Garcia GG | Year | 2002 |
| Journal | J Immunol | Volume | 169 |
| Issue | 9 | Pages | 5021-7 |
| PubMed ID | 12391217 | Mgi Jnum | J:79788 |
| Mgi Id | MGI:2388935 | Doi | 10.4049/jimmunol.169.9.5021 |
| Citation | Garcia GG, et al. (2002) Age-Dependent Defects in TCR-Triggered Cytoskeletal Rearrangement in CD4(+) T Cells. J Immunol 169(9):5021-7 |
| abstractText | Previous research has shown that many of the CD4 T cells from older mice do not form functional immune synapses after conjugation with peptide-pulsed APC. We now show that the defect lies at a very early stage in the cytoskeletal reorganization that precedes movement of protein kinases and their substrates to the TCR/APC interface. Antagonist peptides presented to T cells from young mice induce migration of talin (but not paxillin, vinculin, or F-actin) to the APC contact zone, but CD4 T cells from older donors typically fail to show the talin polarization response. A spreading assay in which contact with anti-CD3-coated slides induces CD4 T cells to assume a conical shape and develop lammelopodia also shows a decline with age in the proportion of T cells that can initiate cytoskeletal changes in response to this simplified stimulus. Finally, the transition from detergent-soluble to cytoskeletal forms of the p16, p21, and p23 isoforms of CD3zeta in response to CD3/CD4/CD28 cross-linking is much stronger in young than in old T cells. Thus, defects in cytoskeletal reorganization triggered by initial contact between TCR and peptide-bearing APC precede, and presumably contribute to, defective activation of protein kinase-mediated signals in the first few minutes of the activation cascade in T cells from aged mice. |
