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, R. A., Peakman, M., Hussain, M. J., Alviggi, L., Watkins, P. J., Leslie, R. D., Vergani, D.
• Format: Journal Article
• Language: English
• Published: American Diabetes Association 01.01.1993
• ISSN: 0012-1797; 1939-327X; 0012-1797
• DOI: 10.2337/diabetes.42.1.127

Increase in simultaneous coexpression of naive and memory lymphocyte markers at diagnosis of IDDM. R A Smerdon , M Peakman , M J Hussain , L Alviggi , P J Watkins , R D Leslie and D Vergani Department of Immunology and Diabetes, King's College School of Medicine and Dentistry, London, UK. Abstract The monoclonal antibodies 2H4 (anti-CD45RA) and UCHL1 (anti-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 and maturation is important in the pathogenesis of the disease.