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  • 1
    ISSN: 1432-0428
    Keywords: Non-obese diabetic mouse ; T cell receptor ; monoclonal antibody ; cyclophosphamide ; insulitis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The expression of specific T-cell receptor gene segments by T lymphocytes appears to be critically important for the induction of several experimental autoimmune diseases mediated by these cells. We examined whether this situation also applied to non-obese diabetic mice by using various T-cell receptor VΒ-specific monoclonal antibodies. No significant age- or sex-related differences were observed in VΒ usage by peripheral and splenic T lymphocytes. CD8+ T lymphocytes among the islet-derived mononuclear cells isolated from 20-week-old female non-obese diabetic mice showed heterogeneity of their VΒ gene usage. In order to examine the role of T lymphocyte subsets expressing specific T-cell receptor VΒ gene segments in the development of diabetes mellitus, T-cell receptor VΒ-specific monoclonal antibodies were administered to 10-week-old male non-obese diabetic mice treated with cyclophosphamide. None of the antibodies used could significantly diminish the incidence of cyclophosphamide-induced diabetes and the severity of insulitis [anti-VΒ3 (11 of 22 mice became diabetic, 50%), anti-VΒ5 (9 of 14, 64%), anti-VΒ8 (9 of 21, 43%), anti-VΒ11 (12 of 23, 52%), anti-VΒ14 (7 of 12, 58%), and anti-VΒ5 + anti-VΒ11 (6 of 12, 50%)] when compared with control mice (12 of 21, 57%). In addition, there were no significant differences in T-cell receptor VΒ usage between diabetic and non-diabetic cyclophosphamide-treated mice. These results suggest that five T-lymphocyte subsets expressing different T-cell receptor VΒ gene segments, considered to be candidates involved in the pathogenesis of autoimmune diabetes, do not individually contribute to the development of cyclophosphamide-induced diabetes in non-obese diabetic mice.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Keywords CD8 T-cell clone ; NOD mice ; scid mice ; transfer of diabetes ; insulitis ; adhesion molecule.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A CD8 T-cell clone (YNK1.3) generated from acutely diabetic NOD mouse islets, showed proliferation and cytotoxicity when challenged with NOD and BALB/c islet cells and NOD-derived insulinoma cells. When 1–2 × 107 YNK1.3 cells were administered to 7–10-day-old NOD mice, the cells transferred overt diabetes very rapidly in each of the 16 recipients within 4 days of cell transfer. However, of 14 recipients receiving YNK 1.3 cells above 14 days of age none became diabetic. Fluorescent dye-labelled YNK1.3 cells extensively accumulated in the islets by 36 h after transfer in 7-day-old NOD recipients, while no significant insulitis was seen in 21-day-old recipients. Over half of NOD-scid recipients (5/9) rapidly became diabetic within 5 days after transfer of 1–2 × 107 YNK1.3 cells at 7 days of age, whereas only one of 12 recipients over 14 days of age became diabetic. Furthermore, YNK1.3 cells also transferred diabetes to H-2Kd-matched very young BALB/c-scid and CB17-scid mice, but not to C57BL/6-scid mice. Thus, optimally activated islet-specific CD8 T-cell clones are able to rapidly transfer diabetes to NOD and MHC class I compatible scid mice when a large enough number is administered at 7 days of age. Administration of monoclonal antibodies against adhesion molecules involved in the trafficking of lymphocytes from the circulation into the inflammatory tissues, could not prevent the cellular infiltration of YNK1.3 cells into the islets in 7-day-old NOD recipients. The results indicate that islet cells in the mouse around 7 days of age are generally susceptible to cytotoxic CD8 T cells, suggesting, therefore, that CD8 T cells may play an important role in the initiation of autoimmune diabetes in NOD mice. [Diabetologia (1997) 40: 1044–1052]
    Type of Medium: Electronic Resource
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