Preincubation with anti-CD4 influences activation of human T cells by subsequent co-cross-linking of CD4 with CD3.
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.
Tsygankov
A Y
AY
Max-Planck-Society, Clinical Research Units for Rheumatology, Erlangen, Germany.
Bröker
B M
BM
Guse
A H
AH
Meinke
U
U
Roth
E
E
Rossmann
C
C
Emmrich
F
F
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
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