Passive Transfer of Lymphocytes From Diabetic Man to Athymic Mouse

Lipsick, Joseph S.; Beattie, Gillian M.; Osler, Abraham G.; Kaplan, Nathan O.; Thurneyssen, O.; Jansen, F. K.; Vialettes, B.; Vague, P; Selam, J. L.; Mirouze, J; Serra, A; Farndon, John; Shenton, BK; Johnston, Ian

doi:10.1016/s0140-6736(79)92246-3

Cited by 16 publications

(4 citation statements)

References 12 publications

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“…Donor nu/+ or conventional BALB/c mice were killed on days 7,9,10,12,13,14,16,17,19,20, and 30 after the initial SZ injection and their spleen cells used for passive transfer.…”

Section: Resultsmentioning

confidence: 99%

“…It must also be noted that our attempts at human to mouse transfer were similarly unsuccessful. 13 The recent report that the injection of dead lymphocytes from SZ-induced diabetic mice leads to insulitis and abnormal glucose tolerance in recipient mice 14 suggests the need to consider alternative facets of the mechanism underlying previously successful findings. The possibility of viral transfer merits serious consideration, particularly in view of the reports that SZ-induced insulitis may be associated with the presence of virus particles in mouse pancreatic islet tissues.…”

Section: Discussionmentioning

confidence: 99%

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Streptozotocin-induced Diabetes in Athymic and Conventional BALB/c MICE

et al. 1980

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Spleen cells from conventional BALB/c or athymic mice with streptozotocin (SZ)-induced hyperglycemia failed to raise blood sugar levels when injected into athymic or thymus-sufficient recipients. Passive transfer efforts were unsuccessful despite variations in donor-recipient pairs with respect to age, thymic function, or time after sensitization of donor mice. Athymic mice develop hyperglycemia following SZ but fail to mount an inflammatory lymphocyte infiltration. In contrast, the heterozygotes show a marked cellular response, which seems to follow the onset of hyperglycemia. The injection of spleen cells from thymus-sufficient mice to athymic recipients confers immunologic competence on the latter as tested by antibody formation to sheep erythrocytes.

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“…Donor nu/+ or conventional BALB/c mice were killed on days 7,9,10,12,13,14,16,17,19,20, and 30 after the initial SZ injection and their spleen cells used for passive transfer.…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Streptozotocin-induced Diabetes in Athymic and Conventional BALB/c MICE

et al. 1980

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“…These observations, although preliminary, appeared to imply that the induction of experimental hyperglycemia in mice is critically mediated by autoreactive immune lymphocytes that recognize, and perhaps destroy, the pancreatic beta cells in an organ-specific species-nonspecific manner. Subsequent efforts in several laboratories to confirm the reports of Buschard and coworkers have been, unfortunately, largely unsuccessful (14)(15)(16)(17)(18).…”

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confidence: 99%

Insulin-dependent diabetes mellitus induced by subdiabetogenic doses of streptozotocin: obligatory role of cell-mediated autoimmune processes.

Paik¹,

Fleischer²,

Shin³

1980

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

150

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The role of thymic functions in the development of insulin-dependent diabetes was investigated in athymic nude (nu/nu) mice and euthymic heterozygous (+/nu) littermates of BALB/c origin treated with streptozotocin. The injection of a single high dose of streptozotocin (200 mg/kg body weight) induced rapid and permanent hyperglycemia in both nu/nu and +/nu mice. In contrast, the injection of the same total dose divided into multiple "subdiabetogenic" doses (40 mg/kg per day for 5 consecutive days) caused the development of delayed but progressive hyperglycemia only in the thymuscompetent +/nu mice. Female mice of either genotype were significantly less susceptible to streptozotocin at both doses. Restoration of thymic immunity in nu/nu mice by thymus grafts also restored the susceptibility to the hyperglycemic effects of multiple low doses of streptozotocin. Moreover, splenic lymphocytes from +/nu mice previously made diabetic with the multiple low-dose injections of streptozotocin induced transient glucose intolerance in nu/nu mice. The ability of the diabetic spleen cells to transfer the diabetic state was abolished when the splenic lymphocytes were depleted of the T cells but not when they were depleted of B cells. These results provide direct proof that thymus-dependent functions play an obligatory etiologic role in the development of diabetes in mice treated with repeated subdiabetogenic doses of streptozotocii. These observations also add to the growing evidence that autoimmune amplification mechanisms may be critically involved in the etiology of juvenile-tnset diabetes mellitus in humans.There is increasing evidence that the development of the juvenile-type insulin-dependent diabetes mellitus is mediated by autoimmune processes. Pancreatic islets of children with newly diagnosed insulin-dependent diabetes frequently contain infiltrating mononuclear lymphocytes (1), and a large fraction of juvenile-onset diabetes patients have both circulating antibodies against the islet cells (2) and lymphocytes with cytolytic activity against human insulinoma cells in culture (3). In addition, epidemiologic studies in several countries have independently established that a number of alleles of the HLA gene complex, especially of the HLA-D locus, are associated with a significantly increased risk of this form of diabetes (reviewed in ref. 4).Evidence implicating autoimmune processes in the etiology of insulin-dependent diabetes comes also from experimental model systems utilizing laboratory rodents. In a series of experiments, Like and Rossini and their coworkers have shown that the induction of diabetes in mice and rats by the beta-cell toxin streptozotocin typically proceeds in two quite different pathways. When a single, sublethal, high dose of streptozotocin was administered to susceptible animals, rapid destruction of the islet beta cells ensued, followed almost immediately by a profound and permanent hyperglycemia (5). In contrast, the administration of the same total dose of streptozotocin, divided into m...

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“…Similarly, there is no evidence that lymphocytes from IDD patients are cytotoxic against pancreatic cells, except in the special case of insulinoma cell culture [6]. The passive transfer of transient diabetes by circulating IDD lymphocytes has been described in one publication [7], but this has not been confirmed by others [8][9][10][11].…”

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Lymphocytes from diabetics suppress insulin releasein vitro

Boîtard

Debray-Sachs

Pouplard³

et al. 1981

Diabetologia

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The insulin response of isolated islet cells to glucose and theophylline in vitro was studied after incubation with lymphocytes. The test was employed to explore cell-mediated immunity in diabetics. A significant inhibition of insulin response to glucose and theophylline as compared to insulin release in a "basal" medium was found after incubation with blood lymphocytes from 21 out of 23 insulin-dependent diabetics (mean secretion index 18 +/- 18 versus 118 + 8 (SEM) % in control subjects). Most of the patients studied had associated autoimmune diseases: all of these displayed inhibition of insulin release. In six cases, the diabetes had a recent onset with no associated autoimmune disease: four of them displayed the same inhibition. No inhibition was found in the 26 control subjects and in seven non-insulin-dependent diabetics (mean secretion index 134 +/- 17 versus 145 +/- 23 (SEM) % in four control subjects). Lymphocytes inhibiting islet cell response were not cytotoxic against mouse fibroblasts. Twenty-two insulin-dependent diabetics showed islet cell antibodies to human and/or mouse pancreatic islets. However, an inhibition of insulin release was found with no detectable islet cell antibodies in one case, and the converse in two cases. Lymphocyte cytotoxicity to islet cells could play a role in the natural history of insulin-dependent diabetes.

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Passive Transfer of Lymphocytes From Diabetic Man to Athymic Mouse

Cited by 16 publications

References 12 publications

Streptozotocin-induced Diabetes in Athymic and Conventional BALB/c MICE

Streptozotocin-induced Diabetes in Athymic and Conventional BALB/c MICE

Insulin-dependent diabetes mellitus induced by subdiabetogenic doses of streptozotocin: obligatory role of cell-mediated autoimmune processes.

Lymphocytes from diabetics suppress insulin releasein vitro

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