Di. Godfrey et al., FLOW CYTOMETRIC STUDY OF T-CELL DEVELOPMENT IN NOD MICE REVEALS A DEFICIENCY IN ALPHA-BETA-TCR(-)CD8(-) THYMOCYTES()CD4(), Journal of autoimmunity, 10(3), 1997, pp. 279-285
As a result of failed induction of T cell tolerance to pancreatic B ce
lls, non-obese diabetic (NOD) mice develop spontaneous autoimmune insu
lin-dependent diabetes mellitus (IDDM). The thymic stroma, which plays
a crucial role in thymic T cell maturation, undergoes extensive prema
ture 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 Bow cytometry
(FACS). These results are described in detail and reveal that most thy
mocyte subsets were normally represented, including alpha beta TcR(-)C
D4(-)CD8(-) (triple negative; TN), alpha beta TcR(-)CD4(-)CD8(-) and a
lpha beta TcR(-)CD4(-)CD8(-) (immature single positive; ISP), alpha be
ta TcR(-/low)CD4(+)CD8(+) (double positive; DP) and alpha beta TcR(+)C
D4(+)CD8(-) and alpha beta TcR(+)CD4(+)CD8(+) (mature single positive;
SP) as well as gamma delta T cells. Kowever, NOD mice exhibited a mar
ked deficiency of thymic alpha beta TcR(+)CD4(-)CD8(-) (alpha beta(+)D
N) T cells. alpha beta(+)DN T cells, which are included among NK1(+) T
cells in C57BL/6 mice, produce large amounts of IL-4 on primary stimu
lation. Given the potential significance of NKT cells in immunoregulat
ion, it is possible that the scarcity of these cells in NOD mice plays
a role in the pathogenesis of IDDM. (C) 1997 Academic Press Limited.