Beta-cell antigen-specific lysis of macrophages by CD4 T-cell clones from newly diagnosed IDDM patient. A putative mechanism of T-cell-mediated autoimmune islet cell destruction.
Immunophenotyping of the early lesion in the pancreatic islets of Langerhans demonstrates a predominance of CD4+ lymphocytes, which may be preceded by an increase in islet macrophages. This observation implies that both types of cells may be involved in autoimmune-mediated beta-cell destruction leading to IDDM. In an attempt to attribute a role to beta-cell antigen-specific CD4-expressing T-cell clones recently isolated from a newly diagnosed IDDM patient, we investigated whether such CD4 T-cells may be pathogenic in an in vitro cytotoxicity assay with HLA-DR-matched antigen-presenting macrophages as target. We report herein that, indeed, beta-cell antigen-specific CD4+ T-cells are capable of lysing macrophages in an antigen-specific fashion. This cytotoxicity is HLA-DR restricted, T-cell receptor complex mediated, and CD4 dependent. These observations imply that both helper T-cells and macrophages may be involved in the disease process via interaction between T-cells and macrophages pulsed with beta-cell antigen.
Roep
B O
BO
Department of Immunohematology, University Hospital, Leiden, The Netherlands.
Kallan
A A
AA
De Vries
R R
RR
D000818:Animals; D015551:Autoimmunity; D015704:CD4 Antigens / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007340:Insulinoma / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D010190:Pancreatic Neoplasms / Q000276:immunology; D051381:Rats; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D015704:CD4 Antigens; D006684:HLA-DR Antigens