Flow cytometric study of T cell development in NOD mice reveals a deficiency in alphabetaTCR+CDR-CD8- thymocytes

As a result of failed induction of T cell tolerance to pancreatic B cells, non-obese diabetic (NOD) mice develop spontaneous autoimmune insulin-dependent diabetes mellitus (IDDM). The thymic stroma, which plays a crucial role in thymic T cell maturation, undergoes extensive premature disorganization in NOD mice, so it is of interest to examine NOD T cell development. In this study, both major and minor developmental populations of thymocytes of NOD/Lt mice were studied and compared to those of BALB/c, C57BL/6 and CBA mice by multiparameter flow cytometry (FACS). These results are described in detail and reveal that most thymocyte subsets were normally represented, including alphaTcR-CD4-CD8- (triple negative; TN), alphabetaTcR-CD4+CD8- and alphabetaTcR-CD4-CD8+ (immature single positive; ISP), alphabetaTcR-/lowCD4+CD8+ (double positive; DP) and alphabetaTcR+CD4+CD8- and alphabetaTcR+CD4-CD8+ (mature single positive; SP) as well as gammadelta T cells. However, NOD mice exhibited a marked deficiency of thymic alphabetaTcR+CD4-CD8- (alphabeta+DN) T cells. alphabeta+DN T cells, which are included among NK1+ T cells in C57BL/6 mice, produce large amounts of IL-4 on primary stimulation. Given the potential significance of NKT cells in immunoregulation, it is possible that the scarcity of these cells in NOD mice plays a role in the pathogenesis of IDDM.