Prolonged islet allograft survival in diabetic nod mice by targeting CD45RB and CD154

Ruth Molano, Antonello Pileggi, Thierry Berney, Raffaella Poggioli, Elsie Zahr, Robert Oliver, Camillo Ricordi, David M. Rothstein, Giacomo P. Basadonna, Luca A Inverardi

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Clinical islet transplantation is a successful procedure that can improve the quality of life in recipients with diabetes. A drawback of the procedure is the need for chronic administration of immunosuppressive drugs that, among other side effects, are potentially diabetogenic. Definition of immunosuppressive protocols that utilize nondiabetogenic compounds could further improve islet transplantation outcome. We used the NOD mouse to assess the effect of targeting the T-lymphocyte surface receptors CD45RB and CD154 in preventing loss of allogeneic islet grafts as a result of recurrence of autoimmunity and allorejection. Administration of the two antibodies led to significantly prolonged allograft survival, with a percentage of grafts surviving longterm. The therapeutic efficacy of the treatment was paralleled by a shift in CD45RB isoform expression on T-lymphocytes, increased in vitro responsiveness to interleukin-7, and increased in vitro γ-interferon production after anti-CD3 antibody stimulation. Furthermore, graft infiltration by CD8+ T-cells was remarkably reduced. Recipient mice bearing functioning allografts were otherwise immunocompetent, as assessed in vivo and in vitro by numerous tests, including intragraft cytokine production, responsiveness to polyclonal stimulation and alloantigens, and analysis of cell subset phenotype. These data show that nondiabetogenic regimens of immunomodulation can lead to prolonged islet allograft survival in the challenging NOD mouse model.

Original languageEnglish
Pages (from-to)957-964
Number of pages8
JournalDiabetes
Volume52
Issue number4
DOIs
StatePublished - Apr 1 2003

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Allografts
Islets of Langerhans Transplantation
Inbred NOD Mouse
Immunosuppressive Agents
T-Lymphocytes
Transplants
Interleukin-7
Isoantigens
Immunomodulation
Autoimmunity
Interferons
Anti-Idiotypic Antibodies
Protein Isoforms
Quality of Life
Cytokines
Phenotype
Recurrence
Antibodies
Pharmaceutical Preparations
In Vitro Techniques

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Molano, R., Pileggi, A., Berney, T., Poggioli, R., Zahr, E., Oliver, R., ... Inverardi, L. A. (2003). Prolonged islet allograft survival in diabetic nod mice by targeting CD45RB and CD154. Diabetes, 52(4), 957-964. https://doi.org/10.2337/diabetes.52.4.957

Prolonged islet allograft survival in diabetic nod mice by targeting CD45RB and CD154. / Molano, Ruth; Pileggi, Antonello; Berney, Thierry; Poggioli, Raffaella; Zahr, Elsie; Oliver, Robert; Ricordi, Camillo; Rothstein, David M.; Basadonna, Giacomo P.; Inverardi, Luca A.

In: Diabetes, Vol. 52, No. 4, 01.04.2003, p. 957-964.

Research output: Contribution to journalArticle

Molano, R, Pileggi, A, Berney, T, Poggioli, R, Zahr, E, Oliver, R, Ricordi, C, Rothstein, DM, Basadonna, GP & Inverardi, LA 2003, 'Prolonged islet allograft survival in diabetic nod mice by targeting CD45RB and CD154', Diabetes, vol. 52, no. 4, pp. 957-964. https://doi.org/10.2337/diabetes.52.4.957
Molano R, Pileggi A, Berney T, Poggioli R, Zahr E, Oliver R et al. Prolonged islet allograft survival in diabetic nod mice by targeting CD45RB and CD154. Diabetes. 2003 Apr 1;52(4):957-964. https://doi.org/10.2337/diabetes.52.4.957
Molano, Ruth ; Pileggi, Antonello ; Berney, Thierry ; Poggioli, Raffaella ; Zahr, Elsie ; Oliver, Robert ; Ricordi, Camillo ; Rothstein, David M. ; Basadonna, Giacomo P. ; Inverardi, Luca A. / Prolonged islet allograft survival in diabetic nod mice by targeting CD45RB and CD154. In: Diabetes. 2003 ; Vol. 52, No. 4. pp. 957-964.
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