Human tonsillar dendritic cell-induced T cell responses: analysis of molecular mechanisms using monoclonal antibodies.
Dendritic cells, isolated from human tonsillar tissue, were found to be potent stimulators of the sodium periodate T cell oxidative mitogenesis reaction. Monoclonal antibodies against CD2, CD4, CD11a, CD18, LFA-3, ICAM-1, class I and class II major histocompatibility complex (MHC) inhibited T cell proliferation in this response, whereas antibodies against CD8, CD11b, CD11c and CD16 had no effect. Further, antibodies against CD2, CD11a, CD18, LFA-3 and ICAM-1 inhibited the early dendritic cell-T cell clustering event which occurs in this cell interaction. In contrast, antibodies against CD4, class I and class II MHC did not inhibit clustering. Studies examining the expression of the respective molecules upon isolated dendritic cells and T cells suggest that anti-LFA-3 and anti-class II MHC antibodies inhibit at the level of the dendritic cell, whereas anti-CD2 and anti-CD4 antibodies inhibit at the level of the T cell. However, antibodies against CD11a, CD18, ICAM-1 and class I MHC may inhibit at either or both cell levels. These findings have enabled us to propose a molecular mechanism for dendritic cell-T cell interaction in oxidative mitogenesis. Dendritic cell-T cell clustering is mediated by bidirectional binding of LFA-1 (CD11a and CD18) and ICAM-1 (involving both molecules on both cell types) and unidirectional binding of CD2 and LFA-3 (involving T cell CD2 and dendritic cell LFA-3). This initial event permits a second interaction of dendritic cell and T cell molecules, involving T cell CD4, class I MHC (possibly at both cellular levels) and dendritic cell class II MHC, which deliver the signal for proliferation.
King
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Bland-Sutton Institute of Pathology, University College and Middlesex School of Medicine, London.
Katz
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D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000943:Antigens, Differentiation / Q000032:analysis; D002449:Cell Aggregation; D002450:Cell Communication; D002458:Cell Fractionation; D003713:Dendritic Cells / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D008213:Lymphocyte Activation; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D015395:Histocompatibility Antigens Class I