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 immune response through binding to CD40. Previous investigations have suggested that insulin-dependent diabetes (IDDM) in both humans and nonobese diabetic 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 autoantibody production (e.g. islet cell cytoplasmic autoantibodies), we analyzed the expression of CD40L on T lymphocytes (CD3+ cells) in a series of individuals with newly diagnosed IDDM (n = 11), nondiabetic relatives of IDDM probands at increased risk for the disease (n = 21; islet cell cytoplasmic autoantibodies positive; Juvenile Diabetes Foundation titer, > or = 20), and healthy controls (n = 13). Both phorbol myristate acetate (PMA)-stimulated and unstimulated peripheral blood mononuclear cells from study subjects were analyzed by flow cytometry with a series of phenotypic antibody markers (CD3, CD40L, and isotype controls). The kinetics of CD3 and CD40L expression on peripheral blood mononuclear cells under PMA-stimulated 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 disease were similar to those in healthy controls (6, 24, and 48 h; all P = NS). These findings do not support abnormal CD40L expression as the mechanism underlying the functional defect(s) in communication between T lymphocytes and antigen-presenting cells that allows for autoantibody production or the inability of individuals to regulate antiself immunity in IDDM.
Ottendorfer
E
E
Department of Pathology, University of Florida College of Medicine, Gainesville 32610, USA.
Ellis
T M
TM
Bahjat
K S
KS
Clare-Salzler
M
M
Atkinson
M A
MA
D000293:Adolescent; D000328:Adult; D017252:CD3 Complex / Q000032:analysis; D019013:CD40 Antigens; D023201:CD40 Ligand; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis*; D012307:Risk Factors; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D017252:CD3 Complex; D019013:CD40 Antigens; D008024:Ligands; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D013755:Tetradecanoylphorbol Acetate