“…This slight increase in CD8 + CD107a + T cells detected in draining lymph nodes is in line with the claim of a low frequency of T cells responding to bm1 antigens (Figure 7). 10.1080/19420862.2018.1502127-F0007Figure 7.NK cell depletion increases donor alloantigen specific CD8 + T cells expressing CD107a.At the time of rejection initiation in NK-cell depleted mice, 1.5 × 10 5 cells from non-draining and draining pLNs (axillar and brachial) were isolated from syngeneic or allogeneic bm1 skin grafted treated either with isotype control or anti-NK1.1 antibody. Then, syngeneic and allogeneic lymphocytes were re-stimulated in vitro with 0.5 × 10 5 allogeneic syngeneic control and bm1 allogeneic mature BM-DC per well for 1 hour in the presence of PE-conjugated isotype control or PE-conjugated anti-CD107a mAb.…”
Section: Resultsmentioning
confidence: 99%
“…Then, syngeneic and allogeneic lymphocytes were re-stimulated in vitro with 0.5 × 10 5 allogeneic syngeneic control and bm1 allogeneic mature BM-DC per well for 1 hour in the presence of PE-conjugated isotype control or PE-conjugated anti-CD107a mAb. Finally, the Golgi plug monensin was added and incubated 4 more hours.…”
Section: Resultsmentioning
confidence: 99%
“…1.5 × 10 5 of draining and non-draining (axillar and brachial) pLNs were isolated around day of rejection from B6 syngeneic or allogeneic bm1 skin grafted mice treated either with isotype control or anti-NK1.1 antibody and then were re-stimulated in vitro with 0.5 × 10 5 of either syngeneic (B6) or allogeneic bm1 mature BM-DC. PE-labelled isotype-matched control (clone Rtk-275, Biolegend) or PE-conjugated anti-CD107a mAb (clone 1D4B, Biolegend) were added to the cell culture and incubated for 1 hour at 37 ºC in 5% CO 2 atmosphere.…”
Section: Methodsmentioning
confidence: 99%
“…This array of germline-encoded inhibitory and activating receptors detects alterations in the molecular composition of the target cells due to infection, malignant transformation or cellular stress, instructing NK cells to respond to altered self. 1,3–5 …”
Section: Introductionmentioning
confidence: 99%
“…Thus, cells expressing MHC class I mismatched molecules or autologous cells lacking self-MHC class I molecules or cells in which self-MHC class I molecules are down-regulated ( missing self-theory ) become targets for NK cell-mediated cytolysis. 5–7 Moreover, lethally irradiated F1 hybrid mice spontaneously reject parental bone marrow cells (BMCs) or hematopoietic cells, a phenomenon against the laws of transplantation named “ hybrid resistance ”, first described by Snell et al, and then confirmed by others. 8–11 …”
Natural killer (NK) cells are a population of innate type I lymphoid cells essential for early anti-viral responses and are known to modulate the course of humoral and cellular-mediated T cell responses. We assessed the role of NK cells in allogeneic CD8 T cell-mediated responses in an immunocompetent mouse model across an MHC class I histocompatibility barrier to determine its impact in therapeutic clinical interventions with polyclonal or monoclonal antibodies (mAbs) targeting lymphoid cells in transplantation. The administration of an NK cell depleting antibody to either CD8 T cell replete or CD8 T cell-depleted naïve C57BL/6 immunocompetent mice accelerated graft rejection. This accelerated rejection response was associated with an in vivo increased cytotoxic activity of CD8 T cells against bm1 allogeneic hematopoietic cells and bm1 skin allografts. These findings show that NK cells were implicated in the control host anti-donor cytotoxic responses, likely by competing for common cell growth factors in both CD8 T cell replete and CD8 T cell-depleted mice, the latter reconstituting in response to lymphopenia. Our data calls for precaution in solid organ transplantation under tolerogenic protocols involving extensive depletion of lymphocytes. These pharmacological biologics with depleting properties over NK cells may accelerate graft rejection and promote aggressive CD8 T cell cytotoxic alloresponses refractory to current immunosuppression.
“…This slight increase in CD8 + CD107a + T cells detected in draining lymph nodes is in line with the claim of a low frequency of T cells responding to bm1 antigens (Figure 7). 10.1080/19420862.2018.1502127-F0007Figure 7.NK cell depletion increases donor alloantigen specific CD8 + T cells expressing CD107a.At the time of rejection initiation in NK-cell depleted mice, 1.5 × 10 5 cells from non-draining and draining pLNs (axillar and brachial) were isolated from syngeneic or allogeneic bm1 skin grafted treated either with isotype control or anti-NK1.1 antibody. Then, syngeneic and allogeneic lymphocytes were re-stimulated in vitro with 0.5 × 10 5 allogeneic syngeneic control and bm1 allogeneic mature BM-DC per well for 1 hour in the presence of PE-conjugated isotype control or PE-conjugated anti-CD107a mAb.…”
Section: Resultsmentioning
confidence: 99%
“…Then, syngeneic and allogeneic lymphocytes were re-stimulated in vitro with 0.5 × 10 5 allogeneic syngeneic control and bm1 allogeneic mature BM-DC per well for 1 hour in the presence of PE-conjugated isotype control or PE-conjugated anti-CD107a mAb. Finally, the Golgi plug monensin was added and incubated 4 more hours.…”
Section: Resultsmentioning
confidence: 99%
“…1.5 × 10 5 of draining and non-draining (axillar and brachial) pLNs were isolated around day of rejection from B6 syngeneic or allogeneic bm1 skin grafted mice treated either with isotype control or anti-NK1.1 antibody and then were re-stimulated in vitro with 0.5 × 10 5 of either syngeneic (B6) or allogeneic bm1 mature BM-DC. PE-labelled isotype-matched control (clone Rtk-275, Biolegend) or PE-conjugated anti-CD107a mAb (clone 1D4B, Biolegend) were added to the cell culture and incubated for 1 hour at 37 ºC in 5% CO 2 atmosphere.…”
Section: Methodsmentioning
confidence: 99%
“…This array of germline-encoded inhibitory and activating receptors detects alterations in the molecular composition of the target cells due to infection, malignant transformation or cellular stress, instructing NK cells to respond to altered self. 1,3–5 …”
Section: Introductionmentioning
confidence: 99%
“…Thus, cells expressing MHC class I mismatched molecules or autologous cells lacking self-MHC class I molecules or cells in which self-MHC class I molecules are down-regulated ( missing self-theory ) become targets for NK cell-mediated cytolysis. 5–7 Moreover, lethally irradiated F1 hybrid mice spontaneously reject parental bone marrow cells (BMCs) or hematopoietic cells, a phenomenon against the laws of transplantation named “ hybrid resistance ”, first described by Snell et al, and then confirmed by others. 8–11 …”
Natural killer (NK) cells are a population of innate type I lymphoid cells essential for early anti-viral responses and are known to modulate the course of humoral and cellular-mediated T cell responses. We assessed the role of NK cells in allogeneic CD8 T cell-mediated responses in an immunocompetent mouse model across an MHC class I histocompatibility barrier to determine its impact in therapeutic clinical interventions with polyclonal or monoclonal antibodies (mAbs) targeting lymphoid cells in transplantation. The administration of an NK cell depleting antibody to either CD8 T cell replete or CD8 T cell-depleted naïve C57BL/6 immunocompetent mice accelerated graft rejection. This accelerated rejection response was associated with an in vivo increased cytotoxic activity of CD8 T cells against bm1 allogeneic hematopoietic cells and bm1 skin allografts. These findings show that NK cells were implicated in the control host anti-donor cytotoxic responses, likely by competing for common cell growth factors in both CD8 T cell replete and CD8 T cell-depleted mice, the latter reconstituting in response to lymphopenia. Our data calls for precaution in solid organ transplantation under tolerogenic protocols involving extensive depletion of lymphocytes. These pharmacological biologics with depleting properties over NK cells may accelerate graft rejection and promote aggressive CD8 T cell cytotoxic alloresponses refractory to current immunosuppression.
BACKGROUND. Recombinant interleukin-2 (rIL-2) immunotherapy is limited by mi-Nicola M. Finnegan, B.A.Mod. crovascular endothelial cell (EC)-targeted injury. The interaction between rIL-2-H. Paul Redmond, F.R.C.S.I. activated lymphoid cells and EC is a possible mechanism of this systemic toxicity. David J. Bouchier-Hayes, F.R.C.S.I. Taurine, a b-amino acid, is known to have several physiologic actions, including the modulation of calcium homeostasis. The aims of this study were to analyze Department of Surgery, Royal College of Sur-the effects of taurine on rIL-2-activated, lymphocyte-mediated EC and tumor cell geons in Ireland, Beaumont Hospital, Dublin, Ireland. cytotoxicity and to investigate the mechanisms of its action. METHODS. IL-2-activated cytotoxicity, mediated by peripheral blood mononuclear cells, against susceptible tumor cell lines and against EC (fresh EC and an EC cell line) in the presence of taurine was assessed. The effects of taurine on lymphocyte [Ca 2/ ] i were assessed by flow cytometry, and the effects of taurine on granzyme activity were assessed by spectrophotometry. RESULTS. The authors' findings indicated that the addition of taurine significantly reduced rIL-2-activated EC cytotoxicity mediated by natural killer cells, without reducing antitumor response. Taurine was also shown to reduce significantly EC lysis mediated by lymphokine-activated killer (LAK) cells, while also significantly increasing tumor cytotoxicity. The authors demonstrated the importance of calcium in the role played by taurine in lymphocyte-mediated cytotoxicity and found that LAK [Ca 2/ ] i following conjugation to EC was enhanced by taurine. They also found that taurine enhanced Ca 2/-dependent granzyme exocytosis from LAK cells. CONCLUSIONS. These findings indicate that taurine may play a dual role in rIL-2 immunotherapy, due to its ability to reduce the vascular injury associated with this therapy while enhancing its antineoplastic activity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
