Early graft-infiltrating lymphocytes are not associated with graft rejection in a mouse model of skin transplantation.

Graft-infiltrating lymphocytes (GILs) play an important role in promoting rejection after organ transplantation. We recently reported that GILs that accumulated up to 3 days post-transplantation did not promote rejection, whereas GILs present 3-5 days post-transplantation promoted rejection in a mouse heart transplantation model. However, the immunological behaviour of GILs in murine skin transplantation remains unclear. GILs were isolated on days 3, 5 or 7 post-transplantation from C57BL/6 (B6) allogeneic skin grafts transplanted onto BALB/c mice. BALB/c Rag2-/- γc-/- mice (BRGs) underwent B6 skin graft transplantation 10 weeks after adoptive transfer of day 3, 5, or 7 GILs. BRGs reconstituted with day 5 or 7 GILs completely rejected B6 grafts. However, when B6 grafts harvested from recipient BALB/c mice on day 5 or 7 were re-transplanted into BRGs, half of the re-transplanted day 5 grafts established long-term survival, although all re-transplanted day 7 grafts were rejected. BRGs reconstituted with day 3 GILs did not reject B6 grafts. Consistently, re-transplantation using day 3 skin grafts resulted in no rejection. Administration of anti-CD25 antibodies did not prevent the phenomenon observed for the day 3 skin grafts. Furthermore, BRGs reconstituted with splenocytes from naïve BALB/c mice immediately rejected the naïve B6 skin grafts and the re-transplanted day 3 B6 grafts, suggesting that day 3 GILs were unable to induce allograft rejection during the rejection process. In conclusion, the immunological role of GILs depends on the time since transplantation. Day 3 GILs had neither protective nor alloreactive effects in the skin transplant model.

Kanazawa R ，Goto R ，Harada T ，Ota T ，Kobayashi N ，Shibuya K ，Ganchiku Y ，Watanabe M ，Zaitsu M ，Kawamura N ，Shimamura T ，Taketomi A ... -  《-》

Functional roles of graft-infiltrating lymphocytes during early-phase post-transplantation in mouse cardiac transplantation models.

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.

Ganchiku Y ，Goto R ，Kanazawa R ，Ota T ，Shibuya K ，Fukasaku Y ，Kobayashi N ，Igarashi R ，Kawamura N ，Zaitsu M ，Watanabe M ，Taketomi A ... -  《-》

Induction of hyperacute rejection of skin allografts by CD8+ lymphocytes.

Yoshimura R ，Chargui J ，Aitouche A ，Veyron P ，Touraine JL ... -  《TRANSPLANTATION》

Anti-TCR mAb induces peripheral tolerance to alloantigens and delays islet allograft rejection in autoimmune diabetic NOD mice.

Deng R ，Khattar M ，Xie A ，Schroder PM ，He X ，Chen W ，Stepkowski SM ... -  《-》

Indirectly Activated Treg Allow Dominant Tolerance to Murine Skin-grafts Across an MHC Class I Mismatch After a Single Donor-specific Transfusion.

Zhang GY ，Hu M ，Watson D ，Wang YM ，Knight JF ，Alexander SI ... -  《-》