Immune responses of diabetic animals

Nichols, William K.; Spellman, J B; Vann, L L; Daynes, Raymond A.

doi:10.1007/bf00423151

Cited by 36 publications

(11 citation statements)

References 23 publications

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“…Some authors have reported direct depression of the immune response and lymphocyte toxicity of streptozotocin, independent of its diabetogenic actions (3,25). The finding that thymocytes from insulin-treated streptozotocin-induced diabetic rats resemble the thymocytes from controls in every respect argues against direct streptozotocin toxicity.…”

Section: Interpretation Of This Value Should Consider That Infused Humentioning

confidence: 99%

Repopulation of the atrophied thymus in diabetic rats by insulin-like growth factor I.

Binz

Joller

Froesch

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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Atrophy of the thymus is one of the consequences of severe insulin deficiency. We describe here that the weight and the architecture of the thymus of diabetic rats is restored towards normal not only by insulin but also by insulin-like growth factor I (IGF-I) treatment. In contrast to insulin, this effect of IGF-I occurs despite persisting hyperglycemia and adrenal hyperplasia. We also investigated the in vivo effect of IGF-I on replication and differentiation of thymocytes from streptozotocin-induced diabetic rats. Thymocytes from diabetic rats incorporated less [3H]thymidine than did thymocytes from healthy rats. Insulin, as well as IGF-I treatment of diabetic rats increased [3H]thymidine incorporation by thymocytes. Flow cytometry of thymocytes labeled with monoclonal antibodies revealed a decreased expression of the Thy-i antigen in diabetic rats compared with control rats. In addition, a major deficiency of thymocytes expressing simultaneously the W3/25 and the Ox8 antigens (corresponding to immature human CD44/CD8+ thymocytes) was observed. These changes were restored towards normal by insulin as well as by IGF-I treatment. The antibody response to a T cell-dependent antigen (bovine serum albumin) was comparable in normal and diabetic rats. We conclude that IGF-I has important effects on the thymocyte number and the presence of CD4+/CD8+ immature cells in the thymus of diabetic rats despite persisting hyperglycemia. However, helper T-cell function for antibody production appears to be preserved even in the severely diabetic state.Insulin deficiency in humans is accompanied by an increased susceptibility to bacterial and mycotic infections. The reason for this is not clear, and results from different studies are inconsistent (for review, see ref. 1). Many of the immunological abnormalities are also observed in experimental diabetes in mice or rats. In streptozotocin-induced diabetic rats, the cellularity of lymphoid organs is diminished; T-cell responses (allograft reactivity and delayed T-cell hypersensitivity), B-cell responses (humoral antibodies), and phagocytic activities have been reported to be impaired (2-5). Insulin administration restores the immune response of diabetic rats toward normal. In hypophysectomized rats, depressed T-and B-cell functions as well as impaired nonspecific immune responses have been reported (6).Hypophysectomized and diabetic rats have decreased insulin-like growth factor I (IGF-I) levels in common and, therefore, may be used to study the effects of IGF-I in vivo.In both models, low levels of IGF-I are accompanied by growth arrest (7,8). The thymus and spleen are smaller and weigh less than in healthy rats of identical body weight (4, 6). IGF-I treatment of hypophysectomized rats and of diabetic rats leads to an increase in body weight and longitudinal bone growth and increases the cell number in primary and secondary lymphatic organs (9).In addition to insulin deficiency, untreated diabetic rats have decreased growth hormone (GH) serum levels and GH receptor number...

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Section: Interpretation Of This Value Should Consider That Infused Humentioning

confidence: 99%

Repopulation of the atrophied thymus in diabetic rats by insulin-like growth factor I.

Binz

Joller

Froesch

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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“…11,12 In rodents, STZ has been reported to affect the immune system, being associated with bone marrow suppression, derangements in leukocyte count (leukopenia), and lymphocyte depletion in the blood and spleen, the mechanisms of which are not completely understood. [13][14][15][16] Direct and irreversible damage to the bone marrow and the early precursors of T cells is seen in STZ-treated mice. 17 Levine et al studied the toxicological effects of STZ in mice and in large animals (dogs and rhesus monkeys), and reported necrosis of lymphoid organs, and bone marrow hypoplasia.…”

Section: Introductionmentioning

confidence: 99%

Streptozotocin-associated lymphopenia in cynomolgus monkeys

Nagaraju

Bertera

Funair

et al. 2014

Islets

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“…Because this regulated transformed endocrine cell line can be transplanted without contaminating passenger leukocytes, we had a unique opportunity to evaluate whether completely allogeneic islet cells can be transplanted under the kidney capsule or s.c. to correct streptozotocin (STZ)-induced diabetes (17) in mice without additional conventional immunosuppression and how resistant such grafts are against forced immune rejection (2, 6, 8-10).…”

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confidence: 99%

Allogeneic β-islet cells correct diabetes and resist immune rejection

Pericin

Althage

Freigang

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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Allogeneic MHC-incompatible organ or cell grafts are usually promptly rejected by immunocompetent hosts. Here we tested allogeneic ␤-islet cell graft acceptance by immune or naïve C57BL͞6 mice rendered diabetic with streptozotocin (STZ). Fully MHC-mismatched insulin-producing growth-regulated ␤-islet cells were transplanted under the kidney capsule or s.c. Although previously or simultaneously primed mice rejected grafts, STZ-treated diabetic mice accepted islet cell grafts, and hyperglycemia was corrected within 2-4 weeks in absence of conventional immunosuppression. Allogeneic grafts that controlled hyperglycemia expressed MHC antigens, were not rejected for >100 days, and resisted a challenge by allogeneic skin grafts or multiple injections of allogeneic cells. Importantly, the skin grafts were rejected in a primary fashion by the grafted and corrected host, indicating neither tolerization nor priming. Such strictly extralymphatic cell grafts that are immunologically largely ignored should be applicable clinically.

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Immune responses of diabetic animals

Cited by 36 publications

References 23 publications

Repopulation of the atrophied thymus in diabetic rats by insulin-like growth factor I.

Repopulation of the atrophied thymus in diabetic rats by insulin-like growth factor I.

Streptozotocin-associated lymphopenia in cynomolgus monkeys

Allogeneic β-islet cells correct diabetes and resist immune rejection

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