Pathogen stimulation history impacts donor-specific CD8+ T cell susceptibility to costimulation/integrin blockade-based therapy

I. R. Badell, W. H. Kitchens, M. E. Wagener, Aron Lukacher, C. P. Larsen, M. L. Ford

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Recent studies have shown that the quantity of donor-reactive memory T cells is an important factor in determining the relative heterologous immunity barrier posed during transplantation. Here, we hypothesized that the quality of T cell memory also potently influences the response to costimulation blockade-based immunosuppression. Using a murine skin graft model of CD8+ memory T cell-mediated costimulation blockade resistance, we elicited donor-reactive memory T cells using three distinct types of pathogen infections. Strikingly, we observed differential efficacy of a costimulation and integrin blockade regimen based on the type of pathogen used to elicit the donor-reactive memory T cell response. Intriguingly, the most immunosuppression-sensitive memory T cell populations were composed primarily of central memory cells that possessed greater recall potential, exhibited a less differentiated phenotype, and contained more multi-cytokine producers. These data, therefore, demonstrate that the memory T cell barrier is dependent on the specific type of pathogen infection via which the donor-reactive memory T cells are elicited, and suggest that the immune stimulation history of a given transplant patient may profoundly influence the relative barrier posed by heterologous immunity during transplantation. Donor-specific T cell memory elicited by three distinct infections influences murine skin allograft survival in response to costimulation blockade-based immunosuppression in a pathogen-dependent manner.

Original languageEnglish (US)
Pages (from-to)3081-3094
Number of pages14
JournalAmerican Journal of Transplantation
Volume15
Issue number12
DOIs
StatePublished - Dec 1 2015

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Integrins
Tissue Donors
T-Lymphocytes
Heterologous Immunity
Immunosuppression
Therapeutics
Infection
Transplantation
Transplants
Skin
Allografts
Cytokines
Phenotype
Population

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Cite this

Badell, I. R. ; Kitchens, W. H. ; Wagener, M. E. ; Lukacher, Aron ; Larsen, C. P. ; Ford, M. L. / Pathogen stimulation history impacts donor-specific CD8+ T cell susceptibility to costimulation/integrin blockade-based therapy. In: American Journal of Transplantation. 2015 ; Vol. 15, No. 12. pp. 3081-3094.
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Pathogen stimulation history impacts donor-specific CD8+ T cell susceptibility to costimulation/integrin blockade-based therapy. / Badell, I. R.; Kitchens, W. H.; Wagener, M. E.; Lukacher, Aron; Larsen, C. P.; Ford, M. L.

In: American Journal of Transplantation, Vol. 15, No. 12, 01.12.2015, p. 3081-3094.

Research output: Contribution to journalArticle

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