Intrathymic islet cell transplantation reduces β-cell autoimmunity and prevents diabetes in NOD/Lt mice

Ivan Gerling, D. V. Serreze, S. W. Christianson, E. H. Leiter

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

Intrathymic transplantation of syngeneic islets into adolescent NOD/Lt mice was performed to establish whether the thymus would serve as an immunoprivileged site for β-cell engraftment, and whether this treatment would prevent the development of diabetes by eliciting tolerance to islet antigens. Intrathymic injection of cells from 200 NOD islets into 4-wk-old female NOD/Lt mice produced a significant reduction in the severity of insulitis at 24 wk of age. Furthermore, diabetes development was strongly suppressed (11% incidence) compared with controls (100% incidence). Both thymus histology and thymic insulin content revealed a rapid loss of the implanted β-cells with <1% remaining 1 wk posttransplantation. Despite the rapid loss of thymus-implanted islet cells, evidence for tolerance induction to islet cell antigens was obtained by adoptive transfer of splenic leukocytes from these mice into NOD-scid/scid recipients. After adoptive transfer of splenic leukocytes from 24-wk-old untreated prediabetic donors, 4 of 5 NOD-scid/scid recipients developed diabetes within 4 wk, and none of the recipients became diabetic after transfer of splenocytes from intrathymic islet-implanted donors. Intrathymic islet transplantation did not lead to reduction of sialitis in females with reduced severity of insulitis, indicating that the protective effect was tissue specific. This also was reflected in adoptive transfer experiments, because equal severity of sialitis was observed in NOD-scid/scid recipients of spleen cells from either islet transplanted or control NOD/Lt mice. In conclusion, the data suggest that intrathymic injection of islet cells prevents diabetes by stimulating immunological tolerance to β-cells.

Original languageEnglish (US)
Pages (from-to)1672-1676
Number of pages5
JournalDiabetes
Volume41
Issue number12
StatePublished - 1992
Externally publishedYes

Fingerprint

Islets of Langerhans Transplantation
Inbred NOD Mouse
Cell Transplantation
Autoimmunity
Islets of Langerhans
Adoptive Transfer
Sialadenitis
Thymus Gland
Leukocytes
Isogeneic Transplantation
Antigens
Injections
Incidence
Histology
Spleen
Insulin
Therapeutics

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

Gerling, I., Serreze, D. V., Christianson, S. W., & Leiter, E. H. (1992). Intrathymic islet cell transplantation reduces β-cell autoimmunity and prevents diabetes in NOD/Lt mice. Diabetes, 41(12), 1672-1676.

Intrathymic islet cell transplantation reduces β-cell autoimmunity and prevents diabetes in NOD/Lt mice. / Gerling, Ivan; Serreze, D. V.; Christianson, S. W.; Leiter, E. H.

In: Diabetes, Vol. 41, No. 12, 1992, p. 1672-1676.

Research output: Contribution to journalArticle

Gerling, I, Serreze, DV, Christianson, SW & Leiter, EH 1992, 'Intrathymic islet cell transplantation reduces β-cell autoimmunity and prevents diabetes in NOD/Lt mice', Diabetes, vol. 41, no. 12, pp. 1672-1676.
Gerling, Ivan ; Serreze, D. V. ; Christianson, S. W. ; Leiter, E. H. / Intrathymic islet cell transplantation reduces β-cell autoimmunity and prevents diabetes in NOD/Lt mice. In: Diabetes. 1992 ; Vol. 41, No. 12. pp. 1672-1676.
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