Regulation of LFA-1-mediated T cell adhesion by CD4.
Heterotypic adhesion of T lymphocytes to monocytes, B lymphocytes, or other target cells is mainly mediated by LFA-1 and CD2 molecules. Low-affinity binding of resting T cells can be transiently up-regulated by cross-linking of CD3. We have previously found that binding of specific ligands to CD4 can down-regulate adhesion of resting T cells to B cells. We now show that the enhanced adhesiveness of CD4+ T cells induced by CD3 cross-linking using plastic-bound anti-CD3 antibody can also be inhibited by several CD4 ligands. i.e. anti-CD4 antibodies, the gp160 env protein of human immunodeficiency virus, as well as by putative CD4 ligands, i.e. synthetic peptides analogous to the gp160-binding site to CD4 (positions 418-434 and 449-464) and a 12-mer synthetic peptide (DR-12) analogous to positions 35-46 of HLA class II beta subunit and including the highly conserved Arg-Phe-Asp-Ser (RFDS) sequence. After CD3 cross-linking, maximal binding of T cells to HLA class II-positive and -negative B cells was similar, although binding to HLA class II-negative B cells was more prolonged. T cells that were passively induced to up-regulate adhesion by binding of a CD11a-specific antibody NKIL16, known to enhance LFA-1-dependent adhesiveness, were less sensitive to the inhibitory effect of the DR-12 peptide, whereas the inhibitory effects of gp160 were preserved. The kinetics of adhesion of NKIL16-pretreated T cells was not influenced by HLA class II expression at the B cell surface. Together, these results strongly suggest that CD4-HLA class II interaction may down-regulate low-affinity adhesion of resting T cells and, to some extent, high-affinity adhesion of T cells actively induced by CD3 cross-linking but not passively induced by an anti-CD11a antibody.
Mazerolles
F
F
INSERM U 132, Hôpital des Enfants Malades, Paris, France.
Hauss
P
P
Barbat
C
C
Figdor
C G
CG
Fischer
A
A
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology; D017252:CD3 Complex; D015704:CD4 Antigens / Q000502:physiology*; D002448:Cell Adhesion; D006684:HLA-DR Antigens / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015704:CD4 Antigens; D006684:HLA-DR Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell