Asialo Gm1+ Cd8+ Cells Play an Important Role in Costimulatory Blockade Resistant Rejection

Trambley, Joel; Bingaman, Adam W.; Lin, Alex T.L.; Larsen, Christian; Tc, Pearson

doi:10.1097/00007890-199904150-00453

Cited by 2 publications

(4 citation statements)

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“…Numerous experimental studies demonstrate that CD8-dependent rejection is resistant to immunoregulation (3)(4)(5)(6)(7)(8)(9)(10)(11). Immunotherapeutic agents, such as anti-CD4 mAb (8,10,12), gallium nitrate (12), anti-CD154 mAb (8,10,13), combined treatment with donor-specific transfusion (DST) and anti-CD154 mAb (14), and CTLA4-Ig (7,8,15), which readily suppress CD4-dependent rejection, have little or no effect on CD8-dependent rejection. Although we have noted activity of this CD8-dependent rejection pathway in response to hepatocellular allografts (3,4,16), this rejection pathway is not unique to hepatocytes.…”

Section: Introductionmentioning

confidence: 99%

“…Although we have noted activity of this CD8-dependent rejection pathway in response to hepatocellular allografts (3,4,16), this rejection pathway is not unique to hepatocytes. The CD8-dependent rejection pathway occurs in response to intestinal allografts (6,7) and has been identified under particular experimental conditions in response to skin allografts (selected host and donor strain combinations) (8,9) and cardiac allografts [selected strain combinations and IFN-c knockout (KO) hosts] (10,11). Furthermore, in humans, immunoresistant CD8 + T cell responses are associated with an increased incidence of acute allograft rejection (17).…”

Section: Introductionmentioning

confidence: 99%

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Activation and Maturation of Alloreactive CD4-Independent, CD8+ Cytolytic T Cells

Lunsford

Horne

Koester

et al. 2006

American Journal of Transplantation

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The goal of this study was to determine the in vivo conditions that promote activation of the (CD4-independent) CD8 + T cell-mediated rejection pathway. We have previously noted that hepatocellular but not islet allografts readily activate this rejection pathway. In the current study, we utilized these two cell transplant models to investigate whether differences in host cell recruitment to the graft site, expression of T-cell activation markers by CD8 + graft infiltrating cells (GICs), and/or development of delayed-type hypersensitivity (DTH) and cytotoxic T lymphocyte cell-mediated effector functions could account for the differential transplant outcomes. The collective results demonstrate that recruitment of CD8 + T cells to the site of transplant, CD103 or CD69 expression on CD8+ GICs, and activation of alloreactive DTH responses are insufficient to initiate CD4-independent, CD8-dependent transplant rejection. Instead, rejection by alloreactive (CD4-independent) CD8 + T cells correlated with expression of CD25, CD154 and CD43 by CD8 + GICs, in vitro alloproliferation by recipient CD8 + T cells, and the development of in vivo allospecific cytolytic effector function. These results suggest that tissue-derived factors influence the activation and maturation of (CD4-independent) CD8 + T cells into cytolytic effectors, which correlates with transplant rejection.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Activation and Maturation of Alloreactive CD4-Independent, CD8+ Cytolytic T Cells

Lunsford

Horne

Koester

et al. 2006

American Journal of Transplantation

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“…However, lymphodepletion leads to the generation of Tmem that are resistant to co-stimulation blockade [14]. Additionally, in rodents [7,33] and nonhuman primate (NHP) [8] allo-tx models, CD8 + Tmem are known to mediate immunosuppression-resistant allograft rejection.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, allo-reactive effector CD4 + and CD8 + Tmem are less susceptible to suppression by regulatory T cells in vivo, than their naïve T cell counterparts [4]. Hence, Tmem are considered a major barrier to improved long-CD4 + Tmem [7,8]. In rodents, multiple viral infections result in the development of CD8 + Tmem that cross-react with allo-antigen (Ag) [9], and mediate resistance to tolerance induction.…”

Section: Introductionmentioning

confidence: 99%

Characterization of eomesodermin and T-bet expression by allostimulated CD8+ T cells of healthy volunteers and kidney transplant patients in relation to graft outcome

Perez‐Gutierrez

Metes

Лу

et al. 2018

Clinical and Experimental Immunology

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Memory T cell (Tmem) responses play a critical role in the outcome of allo‐transplantation. While the role of the T‐box transcription factor Eomesodermin (Eomes) in the maintenance of antigen‐specific Tmem is well studied, little is known about Eomes+CD8+T cell responses after transplantation. We evaluated the phenotype and function of allo‐reactive Eomes+CD8+T cells in healthy volunteers and kidney transplant patients and their relation to transplant outcome. High Eomes expression by steady‐state CD8+T cells correlated with effector and memory phenotype. Following allo‐stimulation, the expression of both the T‐box proteins Eomes and T‐bet by proliferating cells increased significantly, where high expression of Eomes and T‐bet correlated with higher incidence of allo‐stimulated IFNγ+TNFα+ CD8+T cells. In patients with no subsequent rejection, Eomes but not T‐bet expression by donor‐stimulated CD8+T cells, increased significantly after transplantation. This was characterized by increased EomeshiT‐bet‐/lo and decreased Eomes‐/loT‐bethi CD8+T cell subsets, with no significant changes in the EomeshiT‐bethi CD8+T cell subset. No upregulation of exhaustion markers programmed‐death‐1 (PD‐1) and cytotoxic‐T‐lymphocyte‐associated‐antigen‐4 (CTLA4) by donor‐stimulated Eomes+CD8+T cells was observed. Before transplantation, in patients without rejection, there were higher incidences of EomeshiT‐bet‐/lo, and lower incidences of EomeshiT‐bethi and Eomes‐/loT‐bethi donor‐stimulated CD8+T cell subsets, compared to those with subsequent rejection. Overall, our findings indicate that high Eomes expression by allo‐stimulated T‐bet+CD8+T cells is associated with enhanced effector function, and that an elevated incidence of donor‐stimulated CD8+T cells co‐expressing high levels of Eomes and T‐bet before transplantation, may correlate with an increased incidence of acute cellular rejection.

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Asialo Gm1+ Cd8+ Cells Play an Important Role in Costimulatory Blockade Resistant Rejection

Cited by 2 publications

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Activation and Maturation of Alloreactive CD4-Independent, CD8+ Cytolytic T Cells

Activation and Maturation of Alloreactive CD4-Independent, CD8+ Cytolytic T Cells

Characterization of eomesodermin and T-bet expression by allostimulated CD8+ T cells of healthy volunteers and kidney transplant patients in relation to graft outcome

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