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Increased CD69 and Human Leukocyte Antigen-DR Expression on T Lymphocytes in Insulin-Dependent Diabetes Mellitus of Long Standing

University of Vienna, Vienna, Austria

Address all correspondence and requests for reprints to: Alois Gessl, M.D., Division of Endocrinology and Metabolism, Department of Medicine III, University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria. E-mail: alois.gessl{at}akh-wien.ac.at

To better define prevailing activation of circulating T cell subsets in insulin-dependent diabetes mellitus (IDDM) of recent onset (DM; n = 31; median age ± SD,, 28 ± 6.9 yr) and of long standing (DML; 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 -chain (CD25), and CD69 by three-color flow cytometry. Twenty-six healthy subjects (HS; age, 32.0 ± 8.2 yr) served 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.

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