Higher infiltration by Th17 cells compared with regulatory T cells is associated with severe acute T-cell-mediated graft rejection

Chung, Byung Ha; Oh, Hyeyoung; Piao, Shang Guo; Sun, In O; Kang, Seok Hui; Choi, Sun Ryoung; Park, Hoon Suk; Choi, Bum Soon; Choi, Yeong Jin; Park, Cheol Whee; Kim, Yong Soo; Cho, Mi La; Yang, Chul Woo

doi:10.3858/emm.2011.43.11.071

Cited by 30 publications

(36 citation statements)

References 39 publications

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“…In normal individuals, Tregs can modulate auto-immune effector T cell function through suppressive cytokines IL-10, IL-35 and TGFβ (27, 33, 34). This system of Treg-Th17 balance may be deficient in individuals who are undergoing chronic rejection of heart or lung allografts as has been reported in kidney allograft models (35). …”

Section: Introductionmentioning

confidence: 81%

Th17 Responses to Collagen Type V, kα1-Tubulin, and Vimentin Are Present Early in Human Development and Persist Throughout Life

Sullivan

Jankowska‐Gan

Hegde

et al. 2017

American Journal of Transplantation

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Th17-dependent autoimmune responses can develop after heart or lung transplantation, and are associated with fibro-obliterative forms of chronic rejection. However, the specific self-antigens involved are typically different from those associated with autoimmune disease. To investigate the basis of these responses, we questioned whether removal of Tregs or blockade of function reveals a similar auto-antigen bias. We found that Th17 cells specific for collagen type V (Col V), kα-1-tubulin, and vimentin were present in healthy, adult PBMC, cord blood, and fetal thymus. Using synthetic peptides and recombinant fragments of the Col V triple helical region (α1V), we compared Th17 cells from healthy donors with Th17 cells from Col V-reactive heart and lung patients. While the latter responded well to α1(V) fragments and peptides in a DR–restricted fashion, Th17 cells from healthy individuals responded in a DR-restricted fashion to fragments, but not to peptides. Col V, kα-1-tubulin, and vimentin are preferred targets of a highly conserved, hitherto unknown, pre-existing Th17 response that is MHCII-restricted. These data suggest that autoimmunity after heart and lung transplantation may result from dysregulation of an intrinsic mechanism controlling airway and vascular homeostasis.

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Section: Introductionmentioning

confidence: 81%

Th17 Responses to Collagen Type V, kα1-Tubulin, and Vimentin Are Present Early in Human Development and Persist Throughout Life

Sullivan

Jankowska‐Gan

Hegde

et al. 2017

American Journal of Transplantation

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“…In kidney transplantation, Th17 cell infiltration hastens chronic rejection and fibrosis in allograft tissue by promoting lymphoid neogenesis [31]. In our previous report, we demonstrated that higher levels of infiltration of Th17 cells in renal allograft tissue are associated with more severe inflammation and chronic changes in the allograft tissue, and were significantly associated with the progression of interstitial fibrosis and tubular atrophy [32].…”

Section: Discussionmentioning

confidence: 96%

Dysregulation of Th17 Cells during the Early Post-Transplant Period in Patients under Calcineurin Inhibitor Based Immunosuppression

Chung

Kim

et al. 2012

PLoS ONE

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Accumulating evidence suggests that Th17 cells play a role in the development of chronic allograft injury in transplantation of various organs. However, the influence of current immunosuppressants on Th17-associated immune responses has not been fully investigated. We prospectively investigated the changes in Th17 cells in peripheral blood mononuclear cells (PBMCs) collected before and 1 and 3 months after KT in 26 patients and we investigated the suppressive effect of tacrolimus on Th17 in vitro. In the early posttransplant period, the percentage of Th17 cells and the proportion of IL-17-producing cells in the effector memory T cells (TEM) were significantly increased at 3 months after transplantation compared with before transplantation (P<0.05), whereas Th1/Th2 cells and TEM cells were significantly decreased. The degree of increase in Th17 during the early posttransplant period was significantly associated with allograft function at 1 year after transplantation (r = 0.4, P<0.05). In vitro, tacrolimus suppressed Th1 and Th2 cells in a concentration-dependent manner, but did not suppress Th17 cells even at high concentration. This suggests that current immunosuppression based on tacrolimus is inadequate to suppress Th17 cells in KTRs, and dysregulation of Th17 may be associated with the progression of CAD.

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“…[3][4][5] Additionally, CNIs induce undesirable changes in the immune response after kidney transplantation, including a reduction in the proportion and function of CD4 + regulatory T cells (CD4 + Treg cells) within the peripheral blood mononuclear cell (PBMC) population, [6][7][8] and an up-regulation of T helper type 17 (Th17) cell-associated pathways, which are involved in allograft rejection. [9][10][11][12][13][14][15][16][17] Hence, CNI-based immunosuppression may in fact contribute to the progression of chronic allograft dysfunction in kidney transplant recipients (KTRs).…”

Section: Introductionmentioning

confidence: 99%

The effect of mammalian target of rapamycin inhibition on T helper type 17 and regulatory T cell differentiation in vitro and in vivo in kidney transplant recipients

et al. 2014

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SummarySirolimus (SRL) is a promising alternative to calcineurin inhibitors, such as tacrolimus (TAC), in kidney transplant recipients (KTRs), but the immunological benefits of conversion from calcineurin inhibitors to SRL are not fully investigated. In the present study, we evaluated the effect of conversion from TAC to SRL on the T helper type 17/regulatory T (Th17/Treg) axis in three separate studies. First, the effect of SRL on the Th17/Treg axis was evaluated in vitro using peripheral blood mononuclear cells (PBMCs). Second, the effect of conversion from TAC to SRL on the Th17/Treg axis was studied in KTRs. Finally, the effect of SRL on CD8

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Higher infiltration by Th17 cells compared with regulatory T cells is associated with severe acute T-cell-mediated graft rejection

Cited by 30 publications

References 39 publications

Th17 Responses to Collagen Type V, kα1-Tubulin, and Vimentin Are Present Early in Human Development and Persist Throughout Life

Th17 Responses to Collagen Type V, kα1-Tubulin, and Vimentin Are Present Early in Human Development and Persist Throughout Life

Dysregulation of Th17 Cells during the Early Post-Transplant Period in Patients under Calcineurin Inhibitor Based Immunosuppression

The effect of mammalian target of rapamycin inhibition on T helper type 17 and regulatory T cell differentiation in vitro and in vivo in kidney transplant recipients

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