Activation of the classic complement cascade sequence in patients undergoing lung transplantation with and without antithymocyte globulin induction: a comparative study

Pope-Harman, Amy; Magro, Cynthia M.; Ross, Patrick; Kelsey, Moira

doi:10.1016/s1053-2498(02)00840-9

Cited by 2 publications

(2 citation statements)

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“…These antibodies bind to a vast array of antigens found on the cell surface of human T lymphocytes as well as other immune cells [5]. ATG depletes T lymphocytes via classical complement-dependent cell cytotoxicity (CDCC), antibody-dependent cell cytotoxicity (ADCC), opsonization of reactive T cells and the induction of the activation-induced cell death pathway (AICD) [6][7][8][9]. Together, these mechanisms are responsible for the rapid and profound lymphopenia observed in patients treated with ATG.…”

Section: Introductionmentioning

confidence: 99%

Antithymocyte Globulin Inhibits CD8+ T Cell Effector Functions via the Paracrine Induction of PDL-1 on Monocytes

Copic

Direder

Klas

et al. 2023

Cells

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Background: Antithymocyte globulins (ATG) are T cell-depleting antibodies used in solid organ transplantation for induction therapy in sensitized patients with a high risk of graft rejection. Previously described effects besides the depletion of T cells have suggested additional modes of action and identified further cellular targets. Methods: We examined the transcriptional changes arising in immune cells from human blood after ex vivo stimulation with ATG at the single-cell level to uncover additional mechanisms by which ATG regulates T cell activity and effector functions. Findings: Analysis of the paracrine factors present in the plasma of ATG-treated whole blood revealed high levels of chemokines and cytokines, including interferon-γ (IFN-γ). Furthermore, we identified an increase in the surface expression of the programmed death ligand 1 (PDL-1) on monocytes mediated by the released paracrine factors. In addition, we showed that this induction is dependent on the activation of JAK/STAT signaling via the binding of IFN-γ to interferon-γ receptor 1 (IFN-γR1). Lastly, we demonstrated that the modulation of the immune regulatory axis of programmed cell death protein 1 (PD1) on activated CD8+ T cells with PDL-1 found on monocytes mediated by ATG potently inhibits effector functions including the proliferation and granzyme B release of activated T cells. Interpretation: Together, our findings represent a novel mode of action by which ATG exerts its immunosuppressive effects.

show abstract

Section: Introductionmentioning

confidence: 99%

Antithymocyte Globulin Inhibits CD8+ T Cell Effector Functions via the Paracrine Induction of PDL-1 on Monocytes

Copic

Direder

Klas

et al. 2023

Cells

View full text Add to dashboard Cite

show abstract

“…These antibodies bind to a vast array of antigens found on the cell surface of human T lymphocytes as well as other immune cells (5). ATG depletes T lymphocytes via classical complement-dependent cell cytotoxicity (CDCC), antibodydependent cell cytotoxicity (ADCC), opsonization of reactive T cells and the induction of the activation-induced cell death pathway (AICD) (6)(7)(8)(9). Together, these mechanisms are responsible for the rapid and profound lymphopenia observed in patients treated with ATG.…”

Section: Introductionmentioning

confidence: 99%

Antithymocyte globulin inhibits CD8⁺ T cell effector functions via the paracrine induction of PDL-1 on monocytes

Copic

Direder

Klas

et al. 2022

Preprint

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Antithymocyte globulins (ATG) are T cell depleting antibodies used in solid organ transplantation for induction therapy in sensitized patients with high risk of graft rejection. Previously described effects besides depletion of T cells suggest additional modes of action and identified further cellular targets. Here, we examined the transcriptional changes arising in immune cells from human blood after ex vivo stimulation with ATG on a single cell level to uncover additional mechanisms by which ATG regulates T cell activity and effector functions. Analysis of the paracrine factors present in plasma of ATG-treated whole blood revealed high levels of chemokines and cytokines including Interferon-γ (IFN-γ). Furthermore, we identify an increase of surface expression of programmed death ligand 1 (PDL-1) on monocytes mediated by the released paracrine factors. In addition, we show that this induction is dependent on activation of JAK/STAT signaling via binding of IFN-γ to Interferon-γ receptor 1 (IFN-γR1). Lastly, we demonstrate that the modulation of the immune-regulatory axis of Programmed cell death protein 1 (PD-1) on activated CD8+ T cells with PDL-1 found on monocytes mediated by ATG potently inhibits effector functions including proliferation and granzyme B release of activated T cells. Together our findings represent a novel mode of action by which ATG exerts its immunosuppressive effects.

show abstract

Activation of the classic complement cascade sequence in patients undergoing lung transplantation with and without antithymocyte globulin induction: a comparative study

Cited by 2 publications

References 0 publications

Antithymocyte Globulin Inhibits CD8+ T Cell Effector Functions via the Paracrine Induction of PDL-1 on Monocytes

Antithymocyte Globulin Inhibits CD8+ T Cell Effector Functions via the Paracrine Induction of PDL-1 on Monocytes

Antithymocyte globulin inhibits CD8⁺ T cell effector functions via the paracrine induction of PDL-1 on monocytes

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Activation of the classic complement cascade sequence in patients undergoing lung transplantation with and without antithymocyte globulin induction: a comparative study

Cited by 2 publications

References 0 publications

Antithymocyte Globulin Inhibits CD8+ T Cell Effector Functions via the Paracrine Induction of PDL-1 on Monocytes

Antithymocyte Globulin Inhibits CD8+ T Cell Effector Functions via the Paracrine Induction of PDL-1 on Monocytes

Antithymocyte globulin inhibits CD8+ T cell effector functions via the paracrine induction of PDL-1 on monocytes

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Antithymocyte globulin inhibits CD8⁺ T cell effector functions via the paracrine induction of PDL-1 on monocytes