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Interleukin-27 promotes CD8+ T cell reconstitution following antibody-mediated lymphoablation
Katayoun Ayasoufi, … , Robert L. Fairchild, Anna Valujskikh
Katayoun Ayasoufi, … , Robert L. Fairchild, Anna Valujskikh
Published April 4, 2019
Citation Information: JCI Insight. 2019;4(7):e125489. https://doi.org/10.1172/jci.insight.125489.
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Research Article Immunology Transplantation

Interleukin-27 promotes CD8+ T cell reconstitution following antibody-mediated lymphoablation

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Abstract

Antibody-mediated lymphoablation is used in solid organ and stem cell transplantation and autoimmunity. Using murine anti-thymocyte globulin (mATG) in a mouse model of heart transplantation, we previously reported that the homeostatic recovery of CD8+ T cells requires help from depletion-resistant memory CD4+ T cells delivered through CD40-expressing B cells. This study investigated the mechanisms by which B cells mediate CD8+ T cell proliferation in lymphopenic hosts. While CD8+ T cell recovery required MHC class I expression in the host, the reconstitution occurred independently of MHC class I, MHC class II, or CD80/CD86 expression on B cells. mATG lymphoablation upregulated the B cell expression of several cytokine genes, including IL-15 and IL-27, in a CD4-dependent manner. Neither treatment with anti-CD122 mAb nor the use of IL-15Rα–/– recipients altered CD8+ T cell recovery after mATG treatment, indicating that IL-15 may be dispensable for T cell proliferation in our model. Instead, IL-27 neutralization or the use of IL-27Rα–/– CD8+ T cells inhibited CD8+ T cell proliferation and altered the phenotype and cytokine profile of reconstituted CD8+ T cells. Our findings uncover what we believe is a novel role of IL-27 in lymphopenia-induced CD8+ T cell proliferation and suggest that targeting B cell–derived cytokines may increase the efficacy of lymphoablation and improve transplant outcomes.

Authors

Katayoun Ayasoufi, Daniel B. Zwick, Ran Fan, Suheyla Hasgur, Michael Nicosia, Victoria Gorbacheva, Karen S. Keslar, Booki Min, Robert L. Fairchild, Anna Valujskikh

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Figure 2

CD8+ T cell recovery is impaired in heart allograft recipients lacking MHC class I expression.

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CD8+ T cell recovery is impaired in heart allograft recipients lacking M...
B6.CD45.1+ splenic CD8+ T cells were intravenously injected into CD8–/– or TAP1–/– B6 mice (10 × 106 per recipient) followed by BALB/c heart transplantation and mATG treatment. (A) Representative dot plots showing percentages of CD8+CD45.1+ T cells among peripheral blood live cells. (B) The kinetics of CD8+CD45.1+ T cell reconstitution. (C) Numbers of CD8+CD45.1+ T cells in spleen at day 60 after transplant. n = 6 animals per group; error bars represent SD. *P < 0.05, **P < 0.01, ***P < 0.001; ns, P ≥ 0.05 by multiple t tests (B) or Student’s t test (C).

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