Increased expression of T-cell markers of immunological memory associated with protection from type I diabetes. A study of identical twins.
Disturbances in the balance of CD4+ helper T-lymphocytes expressing the surface molecules CD45RA and CD45R0, which define naive and memory populations, respectively, are present at diagnosis of type I diabetes. In a prospective study over 10 years, these subsets were analyzed in samples obtained from 18 identical twins of patients with type I diabetes, 8 of whom became diabetic (prediabetic twins), whereas the rest remained nondiabetic after at least 8 years follow-up and are now unlikely to develop the disease (diabetes-protected twins). At the beginning of the study, percentage levels of naive (CD45RA+) CD4+ lymphocytes were significantly elevated in prediabetic twins compared with diabetes-protected twins (P < 0.05) and remained so throughout the study (P < 0.01). Percentage levels of naive cells in diabetes-protected twins were significantly reduced compared with control subjects both at the beginning and throughout the study (P < 0.05, P < 0.01, respectively). In contrast, diabetes-protected twins at the beginning of the study had elevated percentage levels of memory (CD45R0+) CD4+ lymphocytes that persisted throughout the study compared with prediabetic twins (P < 0.05 for both). Percentage levels of memory cells in prediabetic twins were significantly reduced compared with control subjects both at the beginning and throughout the study (P < 0.01, P < 0.05, respectively). Increased percentage levels of a population of CD4+ lymphocytes coexpressing CD45RA and CD45R0 were seen in both twin groups compared with control subjects at entry into and during the study (P < 0.05 for all), but persisted only in the prediabetic twins.(ABSTRACT TRUNCATED AT 250 WORDS)
Peakman
M
M
Department of Immunology, King's College School of Medicine and Dentistry, London, United Kingdom.
Alviggi
L
L
Hussain
M J
MJ
Lo
S S
SS
Hawa
M
M
Leslie
R D
RD
Vergani
D
D
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D015704:CD4 Antigens / Q000097:blood; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*; D004200:Diseases in Twins; D006801:Humans; D007156:Immunologic Memory; D017493:Leukocyte Common Antigens / Q000097:blood*; D008297:Male; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D012307:Risk Factors; D013601:T-Lymphocytes / Q000276:immunology*; D014430:Twins, Monozygotic
D015703:Antigens, CD; D015415:Biomarkers; D015704:CD4 Antigens; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1