| First Author | Ayasoufi K | Year | 2019 |
| Journal | JCI Insight | Volume | 4 |
| Issue | 7 | PubMed ID | 30944247 |
| Mgi Jnum | J:294256 | Mgi Id | MGI:6454625 |
| Doi | 10.1172/jci.insight.125489 | Citation | Ayasoufi K, et al. (2019) Interleukin-27 promotes CD8+ T cell reconstitution following antibody-mediated lymphoablation. JCI Insight 4(7) |
| abstractText | 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-15Ralpha-/- 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-27Ralpha-/- 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. |
