9295050

pubmed:Citation

8

Naive and memory CD4 T cells differ in cell surface phenotype, function, activation requirements, and modes of regulation. To investigate the molecular bases for the dichotomies between naive and memory CD4 T cells and to understand how the T cell receptor (TCR) directs diverse functional outcomes, we investigated proximal signaling events triggered through the TCR/CD3 complex in naive and memory CD4 T cell subsets isolated on the basis of CD45 isoform expression. Naive CD4 T cells signal through TCR/CD3 similar to unseparated CD4 T cells, producing multiple tyrosine-phosphorylated protein species overall and phosphorylating the T cell-specific ZAP-70 tyrosine kinase which is recruited to the CD3zeta subunit of the TCR. Memory CD4 T cells, however, exhibit a unique pattern of signaling through TCR/CD3. Following stimulation through TCR/CD3, memory CD4 T cells produce fewer species of tyrosine-phosphorylated substrates and fail to phosphorylate ZAP-70, yet unphosphorylated ZAP-70 can associate with the TCR/CD3 complex. Moreover, a 26/28-kDa phosphorylated doublet is associated with CD3zeta in resting and activated memory but not in naive CD4 T cells. Despite these differences in the phosphorylation of ZAP-70 and CD3-associated proteins, the ZAP-70-related kinase, p72syk, exhibits similar phosphorylation in naive and memory T cell subsets, suggesting that this kinase could function in place of ZAP-70 in memory CD4 T cells. These results indicate that proximal signals are differentially coupled to the TCR in naive versus memory CD4 T cells, potentially leading to distinct downstream signaling events and ultimately to the diverse functions elicited by these two CD4 T cell subsets.

eng

IM

MEDLINE

0014-2980

Print

NLM

2094-101

pubmed-meshheading:9295050-Amino Acid Sequence, pubmed-meshheading:9295050-Animals, pubmed-meshheading:9295050-Antibodies, Monoclonal, pubmed-meshheading:9295050-Antigens, CD3, pubmed-meshheading:9295050-CD4-Positive T-Lymphocytes, pubmed-meshheading:9295050-Enzyme Precursors, pubmed-meshheading:9295050-Female, pubmed-meshheading:9295050-Immunologic Memory, pubmed-meshheading:9295050-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:9295050-Mice, pubmed-meshheading:9295050-Mice, Inbred BALB C, pubmed-meshheading:9295050-Peptide Fragments, pubmed-meshheading:9295050-Phosphorylation, pubmed-meshheading:9295050-Protein-Tyrosine Kinases, pubmed-meshheading:9295050-Receptors, Antigen, T-Cell, pubmed-meshheading:9295050-Signal Transduction, pubmed-meshheading:9295050-T-Lymphocyte Subsets, pubmed-meshheading:9295050-Tyrosine, pubmed-meshheading:9295050-Vanadates, pubmed-meshheading:9295050-ZAP-70 Protein-Tyrosine Kinase

Differential T cell receptor-mediated signaling in naive and memory CD4 T cells.

Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't