Functional roles of graft-infiltrating lymphocytes during early-phase post-transplantation in mouse cardiac transplantation models
| Autor: | Yoshikazu Ganchiku, Nozomi Kobayashi, Ryoichi Goto, Ryo Kanazawa, Kazuaki Shibuya, Masaaki Watanabe, Norio Kawamura, Rumi Igarashi, Akinobu Taketomi, Masaaki Zaitsu, Yasutomo Fukasaku, Takuji Ota |
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| Rok vydání: | 2021 |
| Předmět: |
Graft Rejection
Nerve growth factor IB CD3 chemical and pharmacologic phenomena Proinflammatory cytokine Mice Medicine Animals Transplantation Homologous Lymphocytes Transplantation Mice Inbred BALB C biology business.industry CD69 Phenotype Post transplant Mice Inbred C57BL Disease Models Animal surgical procedures operative Immunology biology.protein Heart Transplantation business Early phase |
| Zdroj: | Transplant international : official journal of the European Society for Organ TransplantationReferences. 34(12) |
| ISSN: | 1432-2277 |
| Popis: | Immunological behavior of graft-infiltrating lymphocytes (GILs) determines the graft fate (i.e., rejection or acceptance). Nevertheless, the functional alloreactivity and the phenotype of GILs at various times during the early post-transplantation phase have not been fully elucidated. We examined the immunological activities of early-phase GILs using a murine model of cardiac transplantation. GILs from 120-h allografts, but not 72-h allografts, showed robust activation and produced proinflammatory cytokines. In particular, a significant increase in CD69+ T-bet+ Nur77+ T cells was detected in 120-h allografts. Furthermore, isolated GILs were used to reconstitute BALB/c Rag2-/- γc-/- (BRG) mice. BRG mice reconstituted with 120-h GILs displayed donor-specific immune reactivity and rejected donor strain cardiac allografts; conversely, 72-h GILs exhibited weak anti-donor reactivity and did not reject allografts. These findings were confirmed by re-transplantation of cardiac allografts into BRG mice at 72-h post-transplantation. Re-transplanted allografts continued to function for >100 days, despite the presence of CD3+ GILs. In conclusion, the immunological behavior of GILs considerably differs over time during the early post-transplantation phase. A better understanding of the functional role of early-phase GILs may clarify the fate determination process in the graft-site microenvironment. |
| Databáze: | OpenAIRE |
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