Aberrant Activation of CD8⁺ T-cell and CD8⁺ T-Cell Subsets in Patients With Newly Diagnosed IDDM

Two- and three-color cytofluorimetric techniques were used to study the expression patterns of the activation antigen HLA-DR on peripheral blood immunoregulatory T-cells from 25 patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM) and 14 age- and sex-matched control subjects. The mean percentage of total activated (CD3⁺HLA-DR⁺) T-cells was significantly elevated in the IDDM group compared with the control group (P < 0.001). In control subjects, basal activation of CD4⁺ and CD8⁺ lymphocytes accounted for the low percentage levels of activated T-cells. In contrast, the majority of IDDM patients showed an unbalanced activation of CD4⁺ and CD8⁺ lymphocytes with predominant activation of the CD8⁺ lymphocyte subset. The composition of the activated T-cell fraction was dependent on the composition of the total (activated + nonactivated) T-cell population, as indicated by the positive correlation between the CD4⁺/CD8⁺ T-cell ratios in these two cell populations (r = 0.714; P < 0.001). Excessive activation of CD8⁺ T-cells was attributable to similar increases in the proportions of CD8⁺CD45RA⁺HLA-DR⁺ (naive) and CD8⁺CD45RA⁻HLA-DR⁺ (memory) cells. Analysis of the CD11b-defined subsets revealed predominant activation of CD8⁺ CD11b⁻ (cytotoxic) T-cells; CD8⁺CD16⁺ HLA-DR⁺ natural killer cells wereunchanged. The distribution of HLA-DR⁺ cells among subsets of CD4⁺ T-cells differed from the pattern in the CD8⁺ population in that selective activation of CD4⁺ CD45RA⁻ (memory, helper-inducer) cells accounted for the small increase in activated CD4⁺ cells. The present findings suggest an important role for CD8⁺ T-lymphocytes in IDDM and raise the possibility that these lymphocytes might be the relevant target for early immunotherapy in patients with recent disease onset.