Increase in simultaneous coexpression of naive and memory lymphocyte markers at diagnosis of IDDM.
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.
Smerdon
R A
RA
Department of Immunology and Diabetes, King's College School of Medicine and Dentistry, London, UK.
Peakman
M
M
Hussain
M J
MJ
Alviggi
L
L
Watkins
P J
PJ
Leslie
R D
RD
Vergani
D
D
D000328:Adult; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis*; D017252:CD3 Complex / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000032:analysis*; D008297:Male; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D012016:Reference Values; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013997:Time Factors
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1