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 CD45RO, which define naive and memory populations, respectively, are present at diagnosis of type I diabete s. In a prospective study over 10 years, these subsets were analyzed i n samples obtained from 18 identical twins of patients with type I dia betes, 8 of whom became diabetic (prediabetic twins), whereas the rest remained nondiabetic after at least 8 years followup and are now unli kely to develop the disease (diabetes-protected twins). At the beginni ng of the study, percentage levels of naive (CD45RA(+)) CD4(+) lymphoc ytes were significantly elevated in prediabetic twins compared with di abetes-protected twins (P < 0.05) and remained so throughout the study (P < 0.01). Percentage levels of naive cells in diabetes-protected tw ins mere significantly reduced compared with control subjects both at the beginning and throughout the study (P < 0.05, P < 0.01, respective ly). In contrast, diabetes-protected twins at the beginning of the stu dy had elevated percentage levels of memory (CD45R0(+)) CD4(+) lymphoc ytes that persisted throughout the study compared with prediabetic twi ns (P < 0.05 for both). Percentage levels of memory cells in prediabet ic twins were significantly reduced compared with control subjects bot h at the beginning and throughout the study (P ( 0.01, P < 0.05, respe ctively). Increased percentage levels of a population of CD4(+) lympho cytes coexpressing CD45RA and CD45R0 were seen in both twin groups com pared with control subjects at entry into and during the study (P < 0. 05 for all), but persisted only in the prediabetic twins. In this stud y, we identify for the first time a distinct immune abnormality-overex pression of memory helper T-lymphocytes-that is present in those twins who, despite genetic susceptibility to type I diabetes, do not develo p the disease.