Increase in Simultaneous Coexpression of Naive and Memory Lymphocyte Markers at Diagnosis of IDDM

• Published in: Diabetes (New York, N.Y.) Vol. 42; no. 1; pp. 127 - 133
• Main Authors: Smerdon, Rebecca A, Peakman, Mark, Hussain, Munther J, Alviggi, Lorenzo, Watkins, Peter J, Leslie, R David G, Vergani, Diego
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.01.1993
• Subjects: Adult; Analysis; Antibodies, Monoclonal; Antigens, CD - analysis; Autoimmune diseases; Biological and medical sciences; CD3 Complex - analysis; CD4 Antigens - analysis; CD8 Antigens - analysis; Development and progression; Diabetes Mellitus, Type 1 - immunology; Diabetes. Impaired glucose tolerance; Diagnosis; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Humans; Immunologic Memory; Immunophenotyping; Leukocyte Common Antigens - analysis; Lymphocytes; Male; Medical sciences; Physiological aspects; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Reference Values; T cells; T-Lymphocyte Subsets - immunology; Time Factors; Type 1 diabetes; Endocrinopathy; Autoimmunity; Human; Immunopathology; Immunological memory; Pathogenesis; Biological marker; Autoimmune disease; Activation; Cellular immunity; Phenotype; Cell population; Immunological investigation; T-Lymphocyte; Insulin dependent diabetes
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diab.42.1.127

The monoclonal antibodies 2H4 (antl-CD45RA) and UCHL1 (antl-CD45RO) were used to subdivide the CD4 and CD8 T-cell subsets into naive and memory cells. The peripheral blood lymphocytes of 34 patients with recent-onset IDDM, 21 patients with long-standing IDDM, and healthy control subjects of similar age and sex were analyzed by a three-color immunofluorescence technique. CD4 and CD8 lymphocytes expressed the CD45 isoforms alone (CD45RA+ or CD45RO+) or in combination (CD45RA+RO+). Simultaneous coexpression of both CD45RA and CD45RO (CD45RA+RO+) on CD4 and CD8 lymphocytes in patients with recent-onset IDDM was higher than in control subjects (P < 0.001). The proportion of CD4 lymphocytes expressing CD45RA alone (CD45RA+RO−) was similar in these groups, but the percentage of CD8 lymphocytes that were CD45RA+RO− was significantly higher in the patients with recent-onset IDDM (P < 0.05). The result of these changes is a significant increase in expression of naive phenotypes (CD45RA+ and CD45RA+RO+) on CD4 and CD8 lymphocytes in recent-onset IDDM (P < 0.005 and P < 0.0001). In long-standing IDDM, total CD45RA+ expression on CD4 and CD8 lymphocytes was reduced compared with control subjects (P < 0.05) as a result of a tendency of CD45RA+RO+ and CD45RA+RO+ subsets to be lower. This increase in total naive (CD45RA+) lymphocytes and in coexpression of naive (CD45RA) and memory (CD45RO) markers on CD4 and CD8 lymphocytes subsets In patients with recent-onset IDDM suggests that abnormal regulation of T-cell activation andmaturation is important in the pathogenesis of the disease.