T-lymphopenia and T-cell imbalance in diabetic db/db mice

The diabetic db/db mice of the C57 BL/KsJ strain display anti-islet immunity, thymic dysfunction, and lymphopenia. In the present work, lymphocytes, T-cells, and T-cell subsets were enumerated in thymus and spleen from diabetic db/db mice and their db/ + heterozygote littermates from the 10th day to the 10th month of life. A significant lymphopenia was detected in thymus and spleen from the second month on, involving specifically the T-cell compartment, as assessed by use of a monoclonal anti-Thy1 antibody in indirect fluorescence. The study of T-cell subsets by monoclonal anti-Lyt1 and anti-Lyt2 antibodies revealed a significant increase in Lyt1+ cells and a decrease in Lyt2+ cells, with a corresponding increase of the Lyt1+/Lyt2+ ratio. These anomalies appeared early in life, and were apparently linked neither with the degree of hyperglycemia nor with weight loss or infection. The T-cell depletion in thymus was more pronounced in young male (less than 3 mo) than in young female db/db mice. These alterations may correspond to an increase in the helper/suppressor-cytotoxic ratio and could be linked with the thymic anomalies present in these mice, contributing to the development of anti-islet autoimmunity.