No alteration in T lymphocyte expression of CD40 ligand (CD154) in individuals with or at increased risk for insulin-dependent diabetes mellitus

CD40 ligand (CD40L) regulates multiple phases of the humoral and cellular i mmune response through binding to CD40. Previous investigations have sugges ted that insulin-dependent diabetes (IDDM) in both humans and nonobese diab etic mice may be strongly influenced by similar immunoregulatory molecules. As persons with or at increased risk for the disease are characterized by a number of immunological abnormalities, including that of self-reactive au toantibody production (e.g. islet cell cytoplasmic autoantibodies), we anal yzed the expression of CD40L on T lymphocytes (CD3(+) cells) in a series of individuals with newly diagnosed IDDM (n = II), nondiabetic relatives of I DDM probands at increased risk for the disease (n = 21; islet cell cytoplas mic autoantibodies positive; Juvenile Diabetes Foundation titer, greater th an or equal to 20), and healthy controls (n = 13). Both phorbol myristate a cetate (PMA)-stimulated and unstimulated peripheral blood mononuclear cells from study subjects were analyzed by flow cytometry with a series of pheno typic antibody markers (CD3, CD40L, and isotype controls). The kinetics of CD3 and CD40L expression on peripheral blood mononuclear cells under PMA-st imulated and unstimulated conditions were similar in the three study groups (6, 24, and 48 h; all P = NS). Similarly, unstimulated and PMA stimulated CD40L expressions (percentage of positive cells and level) on CD3(+) cells from newly diagnosed IDDM patients and persons at increased risk for the di sease were similar to those in healthy controls (6, 24, and 48 h; all P = N S). These findings do not support abnormal CD40L expression as the mechanis m underlying the functional defect(s) in communication between T lymphocyte s and antigen-presenting cells that allows for autoantibody production or t he inability of individuals to regulate antiself immunity in IDDM.