Increased CD69 and human leukocyte antigen-DR expression on T lymphocytes in insulin-dependent diabetes mellitus of long standing

To better define prevailing activation of circulating T cell subsets in insulin-dependent diabetes mellitus (IDDM) of recent onset (DM; n = 31; median age +/- SDn, 28 +/- 6.9 yr) and of long standing (DMI; n = 27; age, 33 +/- 10.4 yr; median duration of disease, 105 months), CD4(+) and CD8(+) T cells were analyzed to determine their naive and memory subsets as well as their expression of human leukocyte antigen (HLA)-DR, interleukin-2 receptor alpha-chain (CD25), and CD69 by three-color flow cytometry. Twenty-six healthy subjects (HS; age, 32.0 +/- 8.2 yr) sewed as controls. No deviation was seen in either IDDM group compared to HS in CD25 expression on CD4(+) or CD8(+) cells or in their CD45RA(+) or CD45RA(-) subsets. HLA-DR expression, however, was increased (P < 0.05) in total CD8(+) cells and CD45RA(+) cells, with CD45RA(-) CD8(+) cells joining the prevailing pattern only in DML. Among CD4(+) cells, increased expression of HLA-DR molecules was restricted to total and CD45RA(-) cells in DML. CD69 expression did not differ between IDDM and HS, but differed between DML (CD4(+), CD8(+), and CD45RA(-) CD4(+)) and DM only. In conclusion, our data demonstrate that HLA-DR expression in IDDM is restricted to memory cells (CD45RA(-)) among CD4(+) cells in DML and is more markedly confined to naive (CD45RA(+)) than to memory CD8(+) cells, whereas the early activation antigen CD69 is more readily expressed in DML than in DM. The observed activation of circulating T cells suggests an ongoing immune process in IDDM both at clinical manifestation and after long duration.