title: Preincubation with anti-CD4 influences activation of human T cells by subsequent co-cross-linking of CD4 with CD3.
abstract: Under physiological conditions, T cell activation by major histocompatibility complex (MHC)-antigen complexes requires engagement of both the T cell receptor (TcR) and the CD4 (or CD8) accessory molecules. It has been shown, however, that ligation of CD4 and CD8 can also inhibit T cell activation in an MHC-independent way. Therefore, the role of CD4 in T cell activation and the mechanism of the suppression of T cell functions by anti-CD4 are as yet unclear. We activated T cells by CD4/CD3 co-cross-linking and studied the effect of preincubation with anti-CD4 on this activation. We show here that anti-CD4 effects T cell activation in a complex, time-dependent manner. Whereas short preincubations with anti-CD4 usually enhanced T cell proliferation in response to subsequent co-cross-linking of CD3 with CD4, longer preincubations led to its decrease. The observed suppression of proliferation after a long preincubation with anti-CD4 was apparently due to impairment of TcR signaling, as assessed by measurement of Ca2+ mobilization and tyrosine phosphorylation in T cells. These results add a temporal element to the previously observed synergism between the TcR and CD4 in T cell activation.
authors.affiliation: Max-Planck-Society, Clinical Research Units for Rheumatology, Erlangen, Germany.
authors.forename: A Y
authors.initials: AY
authors.lastname: Tsygankov
authors.forename: B M
authors.initials: BM
authors.lastname: Bröker
authors.forename: A H
authors.initials: AH
authors.lastname: Guse
authors.forename: U
authors.initials: U
authors.lastname: Meinke
authors.forename: E
authors.initials: E
authors.lastname: Roth
authors.forename: C
authors.initials: C
authors.lastname: Rossmann
authors.forename: F
authors.initials: F
authors.lastname: Emmrich
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017252:CD3 Complex / Q000276:immunology* / Q000378:metabolism*; D015704:CD4 Antigens / Q000276:immunology* / Q000378:metabolism* / Q000502:physiology; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000378:metabolism; D004247:DNA / Q000032:analysis / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D015704:CD4 Antigens; D003432:Cross-Linking Reagents; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D014443:Tyrosine; D004247:DNA; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D002118:Calcium