Repopulating T Cells and Alpha1-Antitrypsin Therapy Synergize to Remove the Immunological Barrier to Successful Islet Xenotransplantation

Boris Baranovski; David Ochayon; Peleg Rider; Omer Nisim; Eli Lewis

doi:10.1111/xen.12206

Repopulating T Cells and Alpha1-Antitrypsin Therapy Synergize to Remove the Immunological Barrier to Successful Islet Xenotransplantation

Boris Baranovski, David Ochayon, Peleg Rider, Omer Nisim, Eli Lewis

Research output: Contribution to journal › Meeting Abstract

Abstract

The balance between regulatory T cells and memory T cells is detrimental to xenograft survival. After temporary T cell depletion, T cells repopulate secondary immune organs in a profile that is, to some degree, distinct from the original repertoire prior to depletion, yet falls short of acheving xenograft tolerance. Human α1-antitrypsin (AAT) is an anti-inflammatory and immunomodulatory molecule. AAT allows undeterred purified T cell responses and downplays the levels of local proinflammatory cytokines, two parameters that are critical for Treg expansion. Monotherapy with AAT induces islet allograft tolerance, but fails to induce both skin allograft tolerance and islet xenograft tolerance. However, in combination with temporary T cell depletion, AAT significantly promotes rat-to-mouse islet xenograft acceptance. The mechanism behind this intriguing synergy is unknown.

Original language	English
Article number	728
Pages (from-to)	122-124
Number of pages	3
Journal	Xenotransplantation
Volume	22
Issue number	supplement
DOIs	https://doi.org/10.1111/xen.12206
State	Published - Oct 2015

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title = "Repopulating T Cells and Alpha1-Antitrypsin Therapy Synergize to Remove the Immunological Barrier to Successful Islet Xenotransplantation",

abstract = "The balance between regulatory T cells and memory T cells is detrimental to xenograft survival. After temporary T cell depletion, T cells repopulate secondary immune organs in a profile that is, to some degree, distinct from the original repertoire prior to depletion, yet falls short of acheving xenograft tolerance. Human α1-antitrypsin (AAT) is an anti-inflammatory and immunomodulatory molecule. AAT allows undeterred purified T cell responses and downplays the levels of local proinflammatory cytokines, two parameters that are critical for Treg expansion. Monotherapy with AAT induces islet allograft tolerance, but fails to induce both skin allograft tolerance and islet xenograft tolerance. However, in combination with temporary T cell depletion, AAT significantly promotes rat-to-mouse islet xenograft acceptance. The mechanism behind this intriguing synergy is unknown.",

author = "Boris Baranovski and David Ochayon and Peleg Rider and Omer Nisim and Eli Lewis",

note = "Special Issue: Abstracts of the IPITA‐IXA‐CTS 2015 Joint Congress November 15‐19, 2015, Melbourne, Australia",

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AU - Baranovski, Boris

AU - Ochayon, David

AU - Rider, Peleg

AU - Nisim, Omer

AU - Lewis, Eli

N1 - Special Issue: Abstracts of the IPITA‐IXA‐CTS 2015 Joint Congress November 15‐19, 2015, Melbourne, Australia

PY - 2015/10

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N2 - The balance between regulatory T cells and memory T cells is detrimental to xenograft survival. After temporary T cell depletion, T cells repopulate secondary immune organs in a profile that is, to some degree, distinct from the original repertoire prior to depletion, yet falls short of acheving xenograft tolerance. Human α1-antitrypsin (AAT) is an anti-inflammatory and immunomodulatory molecule. AAT allows undeterred purified T cell responses and downplays the levels of local proinflammatory cytokines, two parameters that are critical for Treg expansion. Monotherapy with AAT induces islet allograft tolerance, but fails to induce both skin allograft tolerance and islet xenograft tolerance. However, in combination with temporary T cell depletion, AAT significantly promotes rat-to-mouse islet xenograft acceptance. The mechanism behind this intriguing synergy is unknown.

AB - The balance between regulatory T cells and memory T cells is detrimental to xenograft survival. After temporary T cell depletion, T cells repopulate secondary immune organs in a profile that is, to some degree, distinct from the original repertoire prior to depletion, yet falls short of acheving xenograft tolerance. Human α1-antitrypsin (AAT) is an anti-inflammatory and immunomodulatory molecule. AAT allows undeterred purified T cell responses and downplays the levels of local proinflammatory cytokines, two parameters that are critical for Treg expansion. Monotherapy with AAT induces islet allograft tolerance, but fails to induce both skin allograft tolerance and islet xenograft tolerance. However, in combination with temporary T cell depletion, AAT significantly promotes rat-to-mouse islet xenograft acceptance. The mechanism behind this intriguing synergy is unknown.

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M3 - Meeting Abstract

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Repopulating T Cells and Alpha1-Antitrypsin Therapy Synergize to Remove the Immunological Barrier to Successful Islet Xenotransplantation

Abstract

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