Increased Numbers ofin vivoActivated T cells in Patients with Recent Onset Insulin-dependent Diabetes Mellitus

Insulin-dependent diabetes mellitus is a T-cell dependent immune mediated disease. Conflicting results regarding the distribution of various T lymphocyte phenotypes in recently diagnosed diabetic patients and in patients with established IDDM compared to controls have been reported. In the present study we evaluated phenotypic characteristics of lymphocytes in IDDM patients. Lymphocytes from 77 newly diagnosed IDDM patients, 58 IDDM patients with disease duration >6 months and 30 non-diabetic controls (including patients with several inflammatory conditions) were analyzed for membrane expression of CD4, CD8, CD45RA, CD45RO and CD27 molecules by FACS analysis. No differences in the percentage of CD8⁺T cells were found between any of the groups. However, the percentage of CD4⁺T cells, and consequently the CD4/CD8 ratio were significantly increased in PBL of recently diagnosed diabetic patients compared to the non-diabetic control group (P<0.005). Interestingly, the fraction of lymphocytes coexpressing CD45RO and CD45RA molecules was significantly increased in recent onset IDDM patients, as well as IDDM patients with disease for a longer duration, compared to controls (P<0.0009 andP<0.007, respectively). IDDM patients had a lower percentage of resting memory T cells (CD45RO⁺CD27⁺) than the non-diabetic controls. The proportion of CD45RO⁺lymphocytes lacking the CD27 molecule ((re)-activated memory cells) was similar in IDDM patients and non-diabetic controls. Our findings confirm and extend previous observations that a disturbance in lymphocyte subset distribution is present in patients with IDDM showing an increase in the percentages of circulating CD4 lymphocytes.