β-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

Abstract

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 β-cell destruction leading to IDDM. In an attempt to attribute a role to β-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, β-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 β-cell antigen.