T-cell migration to vascularized organ allografts

Walch, Jeffrey; Lakkis, Fadi G.

doi:10.1097/mot.0000000000000042

Cited by 8 publications

(4 citation statements)

References 34 publications

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“…The CsA treatment inhibits predominantly production of IL-2, resulting in a lack of T cell proliferation and thereby facilitates donor BMC engraftment. A 7-day immunosuppression protocol combined with BMCs transplantation creates an immune-privileged window for the Treg cells migrations to the immunologically reactive regions (Janssens et al 2003;Walch and Lakkis 2014). Engraftment of donor cells into both the lymphoid and non-lymphoid organs of the recipient presented the Starzl innovatory chimerism theory (Starzl 1971) indicating that only constant contact of the donor cells with the recipient lymphoid organs warrants transplantation tolerance induced by chimerism.…”

Section: Discussionmentioning

confidence: 99%

The Positive Impact of Donor Bone Marrow Cells Transplantation into Immunoprivileged Compartments on the Survival of Vascularized Skin Allografts

Jundziłł

Klimczak

Sönmez

et al. 2021

Arch. Immunol. Ther. Exp.

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Using the vascularized skin allograft (VSA) model, we compared the tolerogenic effects of different allogeneic bone marrow transplantation (BMT) delivery routes into immunoprivileged compartments under a 7-day protocol immunosuppressive therapy. Twenty-eight fully MHC mismatched VSA transplants were performed between ACI (RT1a) donors and Lewis (RT11) recipients in four groups of seven animals each, under a 7-day protocol of alfa/beta TCRmAb/CsA (alpha/beta-TCR monoclonal antibodies/Cyclosporine A therapy). Donor bone marrow cells (BMC) (100 × 106 cells) were injected into three different immunoprivileged compartments: Group 1: Control, without cellular supportive therapy, Group 2: Intracapsular BMT, Group 3: Intragonadal BMT, Group 4: Intrathecal BMT. In Group 2, BMC were transplanted under the kidney capsule. In Group 3, BMC were transplanted into the right testis between tunica albuginea and seminiferous tubules, and in Group 4, cells were injected intrathecally. The assessment included: skin evaluation for signs and grade of rejection and immunohistochemistry for donor cells engraftment into host lymphoid compartments. Donor-specific chimerism for MHC class I (RT1a) antigens and the presence of CD4+/CD25+ T cells were assessed in the peripheral blood of recipients. The most extended allograft survival, 50–78 days, was observed in Group 4 after intrathecal BMT. The T cells CD4+/CD25+ in the peripheral blood were higher after intrathecal BMC injection than other experimental groups at each post-transplant time point. Transplantation of BMC into immunoprivileged compartments delayed rejection of fully mismatched VSA and induction of robust, donor-specific chimerism.

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Section: Discussionmentioning

confidence: 99%

The Positive Impact of Donor Bone Marrow Cells Transplantation into Immunoprivileged Compartments on the Survival of Vascularized Skin Allografts

Jundziłł

Klimczak

Sönmez

et al. 2021

Arch. Immunol. Ther. Exp.

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“…In contrast to the liver tissue transcriptome results, T cell-related transcripts were decreased in blood at the time of ACR. We hypothesize that this is due to the wellknown homing of T cells, particularly CD8 þ T cells, to the transplanted organ at the time of allograft rejection (31). In comparing ACR signatures in tissue and blood, we acknowledge that the use of different microarray platforms presents challenges in drawing firm conclusions.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to the liver tissue transcriptome results, T cell–related transcripts were decreased in blood at the time of ACR. We hypothesize that this is due to the well‐known homing of T cells, particularly CD8 + T cells, to the transplanted organ at the time of allograft rejection .…”

Section: Discussionmentioning

confidence: 99%

Molecular Characterization of Acute Cellular Rejection Occurring During Intentional Immunosuppression Withdrawal in Liver Transplantation

Bonaccorsi‐Riani

Pennycuick

Londoño

et al. 2016

American Journal of Transplantation

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Acute cellular rejection occurs frequently during the first few weeks following liver transplantation. During this period, its molecular phenotype is confounded by peri-and postoperative proinflammatory events. To unambiguously define the molecular profile associated with rejection, we collected sequential biological specimens from 55 patients at least 3 years after liver transplantation who developed rejection during trials of intentional immunosuppression withdrawal. We analyzed liver tissue and blood samples obtained before initiation of drug withdrawal and at rejection, alongside blood samples collected during the weaning process. Gene expression profiling was conducted using whole-genome microarrays and real-time polymerase chain reaction. Rejection resulted in distinct blood and liver tissue transcriptional changes in patients who were either positive or negative for hepatitis C virus (HCV). Gene expression changes were mostly independent from pharmacological immunosuppression, and their magnitude correlated with severity of histological damage. Differential expression of a subset of genes overlapped across all conditions. These were used to define a blood predictive model that accurately identified rejection in HCV-negative, but not HCV-positive, patients. Changes were detectable 1-2 mo before rejection was diagnosed. Our results provide insight into the molecular processes underlying acute cellular rejection in liver transplantation and help clarify the potential utility and limitations of transcriptional biomarkers in this setting.

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“…The use of peripheral blood cells to detect an ongoing rejection response in kidney graft patients is on the basis of the constant migration of alloantigen-primed T cells from the secondary lymphoid tissues to the inflamed allograft [29]. Gene expression profiles by the microarray analysis of RNA isolated from kidney biopsies and peripheral blood lymphocytes had similar expression patterns, supporting the use of peripheral blood as a surrogate to detect ongoing allograft injury [30].…”

Section: Peripheral Bloodmentioning

confidence: 89%

Molecular monitoring of alloimmune-mediated injury in kidney transplant patients

Traitanon¹,

Poggio²,

Fairchild³

2014

Current Opinion in Nephrology and Hypertension

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T-cell migration to vascularized organ allografts

Cited by 8 publications

References 34 publications

The Positive Impact of Donor Bone Marrow Cells Transplantation into Immunoprivileged Compartments on the Survival of Vascularized Skin Allografts

The Positive Impact of Donor Bone Marrow Cells Transplantation into Immunoprivileged Compartments on the Survival of Vascularized Skin Allografts

Molecular Characterization of Acute Cellular Rejection Occurring During Intentional Immunosuppression Withdrawal in Liver Transplantation

Molecular monitoring of alloimmune-mediated injury in kidney transplant patients

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