Abnormal thymocyte maturation in spontaneously diabetic BB rats involves the deletion of CD4-8+ cells.
The object of this study was to further characterize the pathophysiology of the peripheral T lymphopenia in the BB rat. Towards this end, surface markers on unseparated thymocytes and purified thymocyte subsets from age- and sex-matched diabetes-resistant (BBn) and diabetes-prone (BBd) rats were analyzed by two-color flow cytometry. The proportions of thymocytes falling into each of the four main phenotypic subsets were comparable in BBn (n = 9) and BBd (n = 8) rats: respectively, 4.6 +/- 0.6% and 4.4 +/- 0.8%, CD4-8-; 68.1 +/- 1.9% and 71.1 +/- 3.2%, CD4+8+; 18.3 +/- 1.5% and 15.4 +/- 2.3%, CD4+8-; 9.1 +/- 0.9% and 9.1 +/- 1.0%, CD4-8+. In addition, absolute numbers of thymocytes were not significantly different. The levels of expression of CD4, TCR-alpha beta within each thymocyte subset were comparable in BBn and BBd animals as were the anti-TCR-induced proliferative responses of their CD4+8- and CD4-8+ thymocytes. However, phenotypic abnormalities within the CD4-8+ thymocyte subset of the BBd rat were found. A very significant (p less than 0.005) deletion of mature CD4-8+, TCR-alpha beta + thymocytes and a proportional increase (p less than 0.005) of immature CD4-8+, TCR-alpha beta low thymocytes. Moreover, a twofold decrease of CD8 expression by mature CD4-8+ thymocytes was observed in BBd animals. These results suggest that an impaired thymic maturation contributes to the peripheral T lymphopenia of the BBd rat.
McGill Nutrition and Food Science Centre, McGill University, Montreal, Quebec, Canada.
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Plamondon
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Kottis
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Brideau
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Métroz-Dayer
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Poussier
D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D018956:CD5 Antigens; D016827:CD8 Antigens; D002454:Cell Differentiation; D002469:Cell Separation; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D005434:Flow Cytometry; D008213:Lymphocyte Activation; D051381:Rats; D011922:Rats, Mutant Strains; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D018956:CD5 Antigens; D016827:CD8 Antigens; D011948:Receptors, Antigen, T-Cell