Preincubation with anti-CD4 influences activation of human T cells by subsequent co-cross-linking of CD4 with CD3

• Published in: Journal of leukocyte biology Vol. 54; no. 5; pp. 430 - 438
• Main Authors: Tsygankov, Alexander Y., Brӧker, Barbara M., Guse, Andreas H., Meinke, Uta, Roth, Edith, Rossmann, Cornelia, Emmrich, Frank
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Society for Leukocyte Biology 01.11.1993; Federation of American Societies for Experimental Biology
• Subjects: Antibodies, Monoclonal - pharmacology; Biological and medical sciences; Calcium - analysis; Calcium - metabolism; CD3 Complex - immunology; CD3 Complex - metabolism; CD4 Antigens - immunology; CD4 Antigens - metabolism; CD4 Antigens - physiology; Cells, Cultured; Cross-Linking Reagents - metabolism; DNA - analysis; DNA - metabolism; Flow Cytometry; Fluorescent Antibody Technique; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunobiology; intracellular Ca2; Lymphocyte Activation - drug effects; Lymphocyte Activation - physiology; Lymphocyte Specific Protein Tyrosine Kinase p56(lck); Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Phosphorylation; proliferation; Proto-Oncogene Proteins - analysis; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins - physiology; Receptors, Antigen, T-Cell - physiology; T cell clones; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Time Factors; Tyrosine - metabolism; tyrosine phosphorylation; Human; T-Lymphocyte; Activation; Molecular complex; Blocking antibody; Cell subpopulation; Mechanism
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1002/jlb.54.5.430

Under physiological conditions, T cell activation by major histocompatibility complex (MHC)‐anti‐ gen complexes requires engagement of both the T cell receptor (TcR) and the CD4 (or GD8) accessory molecules. It has been shown, however, that ligation of CD4 and GD8 can also inhibit T cell activation in an MHG‐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‐GD4 affects T cell activation in a complex, time‐dependent manner. Whereas short preincubations with anti‐GD4 usually enhanced T cell proliferation in response to subsequent co‐cross‐linking of CDS with GD4, 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.