@article{10.1172/jci.insight.125489, author = {Katayoun Ayasoufi AND Daniel B. Zwick AND Ran Fan AND Suheyla Hasgur AND Michael Nicosia AND Victoria Gorbacheva AND Karen S. Keslar AND Booki Min AND Robert L. Fairchild AND Anna Valujskikh}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {Interleukin-27 promotes CD8+ T cell reconstitution following antibody-mediated lymphoablation}, year = {2019}, month = {4}, volume = {4}, url = {https://insight.jci.org/articles/view/125489}, 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.}, number = {7}, doi = {10.1172/jci.insight.125489}, url = {https://doi.org/10.1172/jci.insight.125489}, }