Ultraviolet light irradiation reduces human islet immunogenicity without altering islet function

P. Y. Benhamou, E. Stein, C. Hober, M. Miyamoto, Y. Watanabe, Y. Nomura, P. C. Watt, Takashi Kenmochi, F. C. Brunicardi, Y. Mullen

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Allograft rejection is the major cause for failure in clinical islet transplantation for diabetic patients. A reduction of donor islet immunogenicity is potentially a useful approach for altering recipient's immune responses. Studies in animal models have shown the immunomodulatory properties of ultraviolet (UV)-B light that are beneficial for allograft survival. However, there is a narrow window between the doses required for immunomodulation and those toxic to β-cells. In addition, this window varies between one species to another. Our study was designed to determine, in vitro, the UV-B dose for human islets that effectively reduces immunogenicity and maintains islet viability and normal function. Islets were isolated from donor pancreas by collagenase digestion and density gradient centrifugation on Euro-Ficoll. Static incubation and perifusion tests were used to measure glucose-stimulated insulin release. Viability was also assessed by histology and function of UV-irradiated islets transplanted under the renal capsule of athymic mice. The immunogenicity of UV-treated islets was determined in vitro with mixed islet lymphocyte culture using healthy human peripheral blood lymphocytes as responders. At a dose of 300 J/m2, both functional assays detected no impairment of insulin release. At 500 J/m2, a slight decrease of stimulated insulin release was observed only in the perifusion system. At the levels of 600 and 900 J/m2, a clear alteration was observed in both basal and stimulated insulin release. Islets irradiated at 300 J/m2 and transplanted into athymic mice stained strongly for insulin and responded to high glucose challenge in in vivo perfusion performed at two weeks. The immunogenicity of UV-irradiated islets was significantly decreased by 43-81% at 300 J/m2 and 51-70% at 500 J/m2. This effect was still present when tested as late as 9 days after irradiation, but only if islets were irradiated immediately after isolation. We conclude that UV-B irradiation at a dose of 300 J/m2 can effectively reduce immunogenicity of human islets without adverse effects on β-cell survival and function. This low dose UV-B irradiation may be a realistic treatment of human islets prior to transplantation.

Original languageEnglish
Pages (from-to)113-120
Number of pages8
JournalHormone and Metabolic Research
Volume27
Issue number3
DOIs
Publication statusPublished - 01-01-1995
Externally publishedYes

Fingerprint

Ultraviolet Rays
Irradiation
Insulin
Lymphocytes
Nude Mice
Dosimetry
Allografts
Tissue Donors
Glucose
Islets of Langerhans Transplantation
Ficoll
Histology
Immunomodulation
Density Gradient Centrifugation
Centrifugation
Poisons
Collagenases
Cell culture
Capsules
Pancreas

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Benhamou, P. Y., Stein, E., Hober, C., Miyamoto, M., Watanabe, Y., Nomura, Y., ... Mullen, Y. (1995). Ultraviolet light irradiation reduces human islet immunogenicity without altering islet function. Hormone and Metabolic Research, 27(3), 113-120. https://doi.org/10.1055/s-2007-979921
Benhamou, P. Y. ; Stein, E. ; Hober, C. ; Miyamoto, M. ; Watanabe, Y. ; Nomura, Y. ; Watt, P. C. ; Kenmochi, Takashi ; Brunicardi, F. C. ; Mullen, Y. / Ultraviolet light irradiation reduces human islet immunogenicity without altering islet function. In: Hormone and Metabolic Research. 1995 ; Vol. 27, No. 3. pp. 113-120.
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abstract = "Allograft rejection is the major cause for failure in clinical islet transplantation for diabetic patients. A reduction of donor islet immunogenicity is potentially a useful approach for altering recipient's immune responses. Studies in animal models have shown the immunomodulatory properties of ultraviolet (UV)-B light that are beneficial for allograft survival. However, there is a narrow window between the doses required for immunomodulation and those toxic to β-cells. In addition, this window varies between one species to another. Our study was designed to determine, in vitro, the UV-B dose for human islets that effectively reduces immunogenicity and maintains islet viability and normal function. Islets were isolated from donor pancreas by collagenase digestion and density gradient centrifugation on Euro-Ficoll. Static incubation and perifusion tests were used to measure glucose-stimulated insulin release. Viability was also assessed by histology and function of UV-irradiated islets transplanted under the renal capsule of athymic mice. The immunogenicity of UV-treated islets was determined in vitro with mixed islet lymphocyte culture using healthy human peripheral blood lymphocytes as responders. At a dose of 300 J/m2, both functional assays detected no impairment of insulin release. At 500 J/m2, a slight decrease of stimulated insulin release was observed only in the perifusion system. At the levels of 600 and 900 J/m2, a clear alteration was observed in both basal and stimulated insulin release. Islets irradiated at 300 J/m2 and transplanted into athymic mice stained strongly for insulin and responded to high glucose challenge in in vivo perfusion performed at two weeks. The immunogenicity of UV-irradiated islets was significantly decreased by 43-81{\%} at 300 J/m2 and 51-70{\%} at 500 J/m2. This effect was still present when tested as late as 9 days after irradiation, but only if islets were irradiated immediately after isolation. We conclude that UV-B irradiation at a dose of 300 J/m2 can effectively reduce immunogenicity of human islets without adverse effects on β-cell survival and function. This low dose UV-B irradiation may be a realistic treatment of human islets prior to transplantation.",
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Benhamou, PY, Stein, E, Hober, C, Miyamoto, M, Watanabe, Y, Nomura, Y, Watt, PC, Kenmochi, T, Brunicardi, FC & Mullen, Y 1995, 'Ultraviolet light irradiation reduces human islet immunogenicity without altering islet function', Hormone and Metabolic Research, vol. 27, no. 3, pp. 113-120. https://doi.org/10.1055/s-2007-979921

Ultraviolet light irradiation reduces human islet immunogenicity without altering islet function. / Benhamou, P. Y.; Stein, E.; Hober, C.; Miyamoto, M.; Watanabe, Y.; Nomura, Y.; Watt, P. C.; Kenmochi, Takashi; Brunicardi, F. C.; Mullen, Y.

In: Hormone and Metabolic Research, Vol. 27, No. 3, 01.01.1995, p. 113-120.

Research output: Contribution to journalArticle

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T1 - Ultraviolet light irradiation reduces human islet immunogenicity without altering islet function

AU - Benhamou, P. Y.

AU - Stein, E.

AU - Hober, C.

AU - Miyamoto, M.

AU - Watanabe, Y.

AU - Nomura, Y.

AU - Watt, P. C.

AU - Kenmochi, Takashi

AU - Brunicardi, F. C.

AU - Mullen, Y.

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Y1 - 1995/1/1

N2 - Allograft rejection is the major cause for failure in clinical islet transplantation for diabetic patients. A reduction of donor islet immunogenicity is potentially a useful approach for altering recipient's immune responses. Studies in animal models have shown the immunomodulatory properties of ultraviolet (UV)-B light that are beneficial for allograft survival. However, there is a narrow window between the doses required for immunomodulation and those toxic to β-cells. In addition, this window varies between one species to another. Our study was designed to determine, in vitro, the UV-B dose for human islets that effectively reduces immunogenicity and maintains islet viability and normal function. Islets were isolated from donor pancreas by collagenase digestion and density gradient centrifugation on Euro-Ficoll. Static incubation and perifusion tests were used to measure glucose-stimulated insulin release. Viability was also assessed by histology and function of UV-irradiated islets transplanted under the renal capsule of athymic mice. The immunogenicity of UV-treated islets was determined in vitro with mixed islet lymphocyte culture using healthy human peripheral blood lymphocytes as responders. At a dose of 300 J/m2, both functional assays detected no impairment of insulin release. At 500 J/m2, a slight decrease of stimulated insulin release was observed only in the perifusion system. At the levels of 600 and 900 J/m2, a clear alteration was observed in both basal and stimulated insulin release. Islets irradiated at 300 J/m2 and transplanted into athymic mice stained strongly for insulin and responded to high glucose challenge in in vivo perfusion performed at two weeks. The immunogenicity of UV-irradiated islets was significantly decreased by 43-81% at 300 J/m2 and 51-70% at 500 J/m2. This effect was still present when tested as late as 9 days after irradiation, but only if islets were irradiated immediately after isolation. We conclude that UV-B irradiation at a dose of 300 J/m2 can effectively reduce immunogenicity of human islets without adverse effects on β-cell survival and function. This low dose UV-B irradiation may be a realistic treatment of human islets prior to transplantation.

AB - Allograft rejection is the major cause for failure in clinical islet transplantation for diabetic patients. A reduction of donor islet immunogenicity is potentially a useful approach for altering recipient's immune responses. Studies in animal models have shown the immunomodulatory properties of ultraviolet (UV)-B light that are beneficial for allograft survival. However, there is a narrow window between the doses required for immunomodulation and those toxic to β-cells. In addition, this window varies between one species to another. Our study was designed to determine, in vitro, the UV-B dose for human islets that effectively reduces immunogenicity and maintains islet viability and normal function. Islets were isolated from donor pancreas by collagenase digestion and density gradient centrifugation on Euro-Ficoll. Static incubation and perifusion tests were used to measure glucose-stimulated insulin release. Viability was also assessed by histology and function of UV-irradiated islets transplanted under the renal capsule of athymic mice. The immunogenicity of UV-treated islets was determined in vitro with mixed islet lymphocyte culture using healthy human peripheral blood lymphocytes as responders. At a dose of 300 J/m2, both functional assays detected no impairment of insulin release. At 500 J/m2, a slight decrease of stimulated insulin release was observed only in the perifusion system. At the levels of 600 and 900 J/m2, a clear alteration was observed in both basal and stimulated insulin release. Islets irradiated at 300 J/m2 and transplanted into athymic mice stained strongly for insulin and responded to high glucose challenge in in vivo perfusion performed at two weeks. The immunogenicity of UV-irradiated islets was significantly decreased by 43-81% at 300 J/m2 and 51-70% at 500 J/m2. This effect was still present when tested as late as 9 days after irradiation, but only if islets were irradiated immediately after isolation. We conclude that UV-B irradiation at a dose of 300 J/m2 can effectively reduce immunogenicity of human islets without adverse effects on β-cell survival and function. This low dose UV-B irradiation may be a realistic treatment of human islets prior to transplantation.

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