Positive signal transduction via surface CD4 molecules does not need coexpression of the CD3/TcR complex.
We previously reported that the human CD4 molecule is capable of transducing a positive signal when activated by an anti-CD4 mAb B66. This antibody, in contrast to many other anti-CD4 mAb, induced IL2 production and proliferation of resting CD4+ peripheral blood T lymphocytes in the absence of any other signal. We further reported that anti-CD4 mAb B66 was able to induce IL2 production in murine T-cell hybridoma cells transfected with full-length human CD4 cDNA. In the present study, we extend these findings by demonstrating that anti-CD4 mAb B66 was able to induce Ca2+ mobilization and IL2 production in a CD3/TcR- variant 31-13, of the CD3/TcR+ Jurkat cell line. We further showed that anti-CD4 mAb B66 was able to activate CD4+ cells from the promonocytic cell line U937. In these cells, mAb B66 induced Ca2+ mobilization when cross-linked with a second antibody and, in addition, the production of large quantities of IL1 beta was measured. In essence, our findings provide direct evidence that cross-linking of CD4 may cause T-cell activation in the absence of the coexpression of the CD3/TcR molecular complex and that, in addition, CD4 might transduce a positive signal in CD4+ cells of the myeloid lineage.
Ludwig Institute for Cancer Research, Lausanne Branch, Epalinges, Switzerland.
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D002051:Burkitt Lymphoma / Q000473:pathology; D017252:CD3 Complex; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D004247:DNA / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology; D051379:Mice; D009000:Monocytes / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015704:CD4 Antigens; D007375:Interleukin-1; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D004247:DNA; D002118:Calcium