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LFA-1-mediated antigen-independent T cell adhesion is regulated by CD4 and p56lck tyrosine kinase.

Authors
  • Mazerolles, F
  • Barbat, C
  • Meloche, S
  • Gratton, S
  • Soula, M
  • Fagard, R
  • Fischer, S
  • Hivroz, C
  • Bernier, J
  • Sekaly, R P
Type
Published Article
Journal
Journal of immunology (Baltimore, Md. : 1950)
Publication Date
Jun 15, 1994
Volume
152
Issue
12
Pages
5670–5679
Identifiers
PMID: 8207199
Source
Medline
License
Unknown

Abstract

We examined the role of CD4 and p56lck in the regulation of LFA-1-dependent T cell adhesion to B cells and to fibroblasts expressing ICAM-1 and HLA-DR by using various transfectant constructions. Although CD4 transfection in CD4low HUT78 T cell lines did not significantly modify their maximal binding to B cells and fibroblasts, it made the LFA-1-dependent adhesion sensitive to inhibition by anti-CD4 Ab, HIV-1 (env) gp 160, and a 12-mer peptide encompassing the 35-46 sequence of the beta 1 domain of the MHC class II molecule. CD4low HUT78 T cell adhesion to B cells was stable over 60 min, whereas expression of CD4 led to a transient adhesion. In addition, adhesion of CD4+ T cells to MHC class II- B cells was also stable. The CD4-dependent alteration of adhesion required the association of CD4 with p56lck because expression of mutant forms of CD4 unable to bind p56lck resulted in a lack of CD4-dependent regulation of adhesion. Herbimycin A, an inhibitor of tyrosine kinase activity, reversed the effect of CD4 transfection on adhesion. These results indicate that ligand binding to CD4 delivers a signal-inducing cell dissociation by activating p56lck tyrosine kinase. This regulatory pathway may provide a quick and reliable way for multiple and subsequent Ag-independent adhesion events of CD4+ T cells.

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