Effect of anti-Ia antibodies, culture, and cyclosporin on prolongation of canine islet allograft survival

Rodolfo Alejandro, Z. Latif, J. Noel, F. L. Shienvold, D. H. Mintz

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Evidence in rodents suggests that islet pretreatment to reduce islet immunogenicity will also require some form of immunosuppression of the recipient for islet allograft acceptance in highly reactive donor-recipient pairs. We attempted to ascertain whether outbred dogs would also require treatment of both donor islets and the recipient to prolong islet allograft survival. Untreated canine islets are uniformly rejected in 6-10 days in beagles. Tissue culture alone, at 37°C for 7 days, or treatment of freshly prepared islets with anti-Ia monoclonal antibodies (MoAbs) (B1F6 + 7.2) did not prolong canine islet allograft survival. Treatment of culture-maintained canine islets with anti-Ia MoAbs plus complement resulted in prolongation of islet allograft survival for 188 and 368 days in two of seven pancreatectomized nonimmunosuppressed beagles. The administration of low doses of cyclosporin A (CsA) intramuscularly, to recipients of untreated canine islet allografts had no effect on graft survival. By contrast, six of nine CsA-treated recipients of islets that were also treated with anti-Ia MoAbs (B1F6 + 7.2) plus complement showed prolongation of graft survival. Euglycemia was sustained for 19, 34, 89, and 300 days after the CsA was discontinued (day 30) in four of these animals. Two animals had unstable grafts from the beginning that failed 23 and 29 days after transplantation. Our results indicate that simple maneuvers like short-term tissue culture at 37°C and treatment of freshly isolated islets with anti-Ia MoAbs and complement are inadequate to prevent rejection in outbred pancreatectomized beagles. In contrast, low-dosage CsA acts synergistically with the in vitro treatment of islets with anti-Ia MoAbs to prolong islet allograft survival in outbred dogs with induced diabetes mellitus.

Original languageEnglish
Pages (from-to)269-273
Number of pages5
JournalDiabetes
Volume36
Issue number3
StatePublished - Dec 1 1987

Fingerprint

Cyclosporine
Allografts
Canidae
Anti-Idiotypic Antibodies
Monoclonal Antibodies
Graft Survival
Dogs
Therapeutics
Immunosuppression
Rodentia
Diabetes Mellitus
Transplantation
Transplants

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

Alejandro, R., Latif, Z., Noel, J., Shienvold, F. L., & Mintz, D. H. (1987). Effect of anti-Ia antibodies, culture, and cyclosporin on prolongation of canine islet allograft survival. Diabetes, 36(3), 269-273.

Effect of anti-Ia antibodies, culture, and cyclosporin on prolongation of canine islet allograft survival. / Alejandro, Rodolfo; Latif, Z.; Noel, J.; Shienvold, F. L.; Mintz, D. H.

In: Diabetes, Vol. 36, No. 3, 01.12.1987, p. 269-273.

Research output: Contribution to journalArticle

Alejandro, R, Latif, Z, Noel, J, Shienvold, FL & Mintz, DH 1987, 'Effect of anti-Ia antibodies, culture, and cyclosporin on prolongation of canine islet allograft survival', Diabetes, vol. 36, no. 3, pp. 269-273.
Alejandro, Rodolfo ; Latif, Z. ; Noel, J. ; Shienvold, F. L. ; Mintz, D. H. / Effect of anti-Ia antibodies, culture, and cyclosporin on prolongation of canine islet allograft survival. In: Diabetes. 1987 ; Vol. 36, No. 3. pp. 269-273.
@article{dcccf6cacf9a49938c835748424eb984,
title = "Effect of anti-Ia antibodies, culture, and cyclosporin on prolongation of canine islet allograft survival",
abstract = "Evidence in rodents suggests that islet pretreatment to reduce islet immunogenicity will also require some form of immunosuppression of the recipient for islet allograft acceptance in highly reactive donor-recipient pairs. We attempted to ascertain whether outbred dogs would also require treatment of both donor islets and the recipient to prolong islet allograft survival. Untreated canine islets are uniformly rejected in 6-10 days in beagles. Tissue culture alone, at 37°C for 7 days, or treatment of freshly prepared islets with anti-Ia monoclonal antibodies (MoAbs) (B1F6 + 7.2) did not prolong canine islet allograft survival. Treatment of culture-maintained canine islets with anti-Ia MoAbs plus complement resulted in prolongation of islet allograft survival for 188 and 368 days in two of seven pancreatectomized nonimmunosuppressed beagles. The administration of low doses of cyclosporin A (CsA) intramuscularly, to recipients of untreated canine islet allografts had no effect on graft survival. By contrast, six of nine CsA-treated recipients of islets that were also treated with anti-Ia MoAbs (B1F6 + 7.2) plus complement showed prolongation of graft survival. Euglycemia was sustained for 19, 34, 89, and 300 days after the CsA was discontinued (day 30) in four of these animals. Two animals had unstable grafts from the beginning that failed 23 and 29 days after transplantation. Our results indicate that simple maneuvers like short-term tissue culture at 37°C and treatment of freshly isolated islets with anti-Ia MoAbs and complement are inadequate to prevent rejection in outbred pancreatectomized beagles. In contrast, low-dosage CsA acts synergistically with the in vitro treatment of islets with anti-Ia MoAbs to prolong islet allograft survival in outbred dogs with induced diabetes mellitus.",
author = "Rodolfo Alejandro and Z. Latif and J. Noel and Shienvold, {F. L.} and Mintz, {D. H.}",
year = "1987",
month = "12",
day = "1",
language = "English",
volume = "36",
pages = "269--273",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "3",

}

TY - JOUR

T1 - Effect of anti-Ia antibodies, culture, and cyclosporin on prolongation of canine islet allograft survival

AU - Alejandro, Rodolfo

AU - Latif, Z.

AU - Noel, J.

AU - Shienvold, F. L.

AU - Mintz, D. H.

PY - 1987/12/1

Y1 - 1987/12/1

N2 - Evidence in rodents suggests that islet pretreatment to reduce islet immunogenicity will also require some form of immunosuppression of the recipient for islet allograft acceptance in highly reactive donor-recipient pairs. We attempted to ascertain whether outbred dogs would also require treatment of both donor islets and the recipient to prolong islet allograft survival. Untreated canine islets are uniformly rejected in 6-10 days in beagles. Tissue culture alone, at 37°C for 7 days, or treatment of freshly prepared islets with anti-Ia monoclonal antibodies (MoAbs) (B1F6 + 7.2) did not prolong canine islet allograft survival. Treatment of culture-maintained canine islets with anti-Ia MoAbs plus complement resulted in prolongation of islet allograft survival for 188 and 368 days in two of seven pancreatectomized nonimmunosuppressed beagles. The administration of low doses of cyclosporin A (CsA) intramuscularly, to recipients of untreated canine islet allografts had no effect on graft survival. By contrast, six of nine CsA-treated recipients of islets that were also treated with anti-Ia MoAbs (B1F6 + 7.2) plus complement showed prolongation of graft survival. Euglycemia was sustained for 19, 34, 89, and 300 days after the CsA was discontinued (day 30) in four of these animals. Two animals had unstable grafts from the beginning that failed 23 and 29 days after transplantation. Our results indicate that simple maneuvers like short-term tissue culture at 37°C and treatment of freshly isolated islets with anti-Ia MoAbs and complement are inadequate to prevent rejection in outbred pancreatectomized beagles. In contrast, low-dosage CsA acts synergistically with the in vitro treatment of islets with anti-Ia MoAbs to prolong islet allograft survival in outbred dogs with induced diabetes mellitus.

AB - Evidence in rodents suggests that islet pretreatment to reduce islet immunogenicity will also require some form of immunosuppression of the recipient for islet allograft acceptance in highly reactive donor-recipient pairs. We attempted to ascertain whether outbred dogs would also require treatment of both donor islets and the recipient to prolong islet allograft survival. Untreated canine islets are uniformly rejected in 6-10 days in beagles. Tissue culture alone, at 37°C for 7 days, or treatment of freshly prepared islets with anti-Ia monoclonal antibodies (MoAbs) (B1F6 + 7.2) did not prolong canine islet allograft survival. Treatment of culture-maintained canine islets with anti-Ia MoAbs plus complement resulted in prolongation of islet allograft survival for 188 and 368 days in two of seven pancreatectomized nonimmunosuppressed beagles. The administration of low doses of cyclosporin A (CsA) intramuscularly, to recipients of untreated canine islet allografts had no effect on graft survival. By contrast, six of nine CsA-treated recipients of islets that were also treated with anti-Ia MoAbs (B1F6 + 7.2) plus complement showed prolongation of graft survival. Euglycemia was sustained for 19, 34, 89, and 300 days after the CsA was discontinued (day 30) in four of these animals. Two animals had unstable grafts from the beginning that failed 23 and 29 days after transplantation. Our results indicate that simple maneuvers like short-term tissue culture at 37°C and treatment of freshly isolated islets with anti-Ia MoAbs and complement are inadequate to prevent rejection in outbred pancreatectomized beagles. In contrast, low-dosage CsA acts synergistically with the in vitro treatment of islets with anti-Ia MoAbs to prolong islet allograft survival in outbred dogs with induced diabetes mellitus.

UR - http://www.scopus.com/inward/record.url?scp=0023573147&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023573147&partnerID=8YFLogxK

M3 - Article

C2 - 3100370

AN - SCOPUS:0023573147

VL - 36

SP - 269

EP - 273

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 3

ER -