PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 33883257-3 2021 METHOD: In this study, we evaluated the roles of amino acids and the Rag complex in regulating mammalian target of rapamycin complex 1 (mTORC1) signaling in CD8+ TILs. Sirolimus 115-124 CD8a molecule Homo sapiens 157-160 33512760-4 2021 We demonstrate that RAPA mitigates GVHD by decreasing T-cell engraftment and differentiation, inhibiting CD8+ T-cell activation and increasing the long-term IL-2 secretion, thereby supporting regulatory T-cell (Treg) proliferation. Sirolimus 20-24 CD8a molecule Homo sapiens 105-108 33512760-6 2021 Importantly, we found that RAPA impact on Treg and CD8+ T cells was closely dependent upon IL-2 signaling and that therapeutic options interfering with IL-2, such as calcineurin inhibitors, antagonize the IL-2-dependent promotion of Treg mediated by RAPA. Sirolimus 27-31 CD8a molecule Homo sapiens 51-54 31408438-9 2019 Administration of sirolimus significantly attenuated CD8+ T cell activation and decreased VEGF-A levels. Sirolimus 18-27 CD8a molecule Homo sapiens 53-56 31541182-1 2021 Mechanistic target of rapamycin complex 1 (mTORC1) regulates CD8+ T-cell differentiation and function. Sirolimus 22-31 CD8a molecule Homo sapiens 61-64 33013932-7 2020 In addition, rapamycin abrogated the ability of both DC subtypes to promote the proliferation and differentiation of IFN-y and Granzyme B producing CD8 + T cells. Sirolimus 13-22 CD8a molecule Homo sapiens 148-151 27466155-4 2016 In this study we showed that rapamycin treatment on RSV-infected murine bone marrow-derived DC (BMDC) decreases the frequency of CD8(+)CD44(high) T cells. Sirolimus 29-38 CD8a molecule Homo sapiens 129-132 30710341-4 2019 Researchers report that rapamycin, a selective mTOR inhibitor, and immunosuppressive agent, has surprising immunostimulatory effects on inducing both quantitative and qualitative aspects of virus-specific memory CD8+ T-cells differentiation and homeostasis in a T-cell-intrinsic manner. Sirolimus 24-33 CD8a molecule Homo sapiens 212-215 30228949-8 2018 Furthermore, rapamycin uniquely enhanced the number and function of CD8+ effector and central memory T cells in a model of long-term contact hypersensitivity provided that rapamycin was present during the antigen sensitization phase. Sirolimus 13-22 CD8a molecule Homo sapiens 68-71 26921303-5 2016 The aim of this study was to evaluate the influence of the immunosuppressive drugs cyclosporine A (CsA) and rapamycin (RAPA) on the level, suppressor properties, and phenotype of human CD8(+)CD28(-) T cells in vitro. Sirolimus 108-117 CD8a molecule Homo sapiens 185-188 26921303-5 2016 The aim of this study was to evaluate the influence of the immunosuppressive drugs cyclosporine A (CsA) and rapamycin (RAPA) on the level, suppressor properties, and phenotype of human CD8(+)CD28(-) T cells in vitro. Sirolimus 119-123 CD8a molecule Homo sapiens 185-188 26921303-7 2016 It was observed that CD8(+)CD28(-) T cells from cultures with CsA or RAPA had similar suppressor properties to cells from control cultures, although the drugs influenced the expression of FOXP3. Sirolimus 69-73 CD8a molecule Homo sapiens 21-24 31191530-9 2019 Using cytomegalovirus (CMV) as model, our next-generation Rapamycin-treated (Rapa-)TCP showed consistently increased proportions of CD4+ T-cells as well as CD4+ and CD8+ central-memory T-cells (TCM). Sirolimus 58-67 CD8a molecule Homo sapiens 165-168 30867239-5 2019 Using supraphysiological stimulation of 4-1BB in the boost phase of a prime-boost immunization, we show that the effect of 4-1BB on Trm generation requires local delivery of both Ag and costimulation, is inhibited by rapamycin treatment during secondary CD8 effector T cell expansion, and is dependent on the signaling adaptor TRAF1. Sirolimus 217-226 CD8a molecule Homo sapiens 254-257 30619313-3 2018 Underlying mechanisms of this observation, particularly the effect of sirolimus on naive- and CMV-specific cytotoxic CD8+ T-cell (CMV-CTL) functionality is still undiscovered. Sirolimus 70-79 CD8a molecule Homo sapiens 117-120 29551338-19 2018 Sirolimus expanded CD4+CD25+FoxP3+ regulatory T cells and CD8+ memory T-cell populations and inhibited interleukin-4 and interleukin-17 production by CD4+ and CD4-CD8- double-negative T cells after 12 months. Sirolimus 0-9 CD8a molecule Homo sapiens 58-61 29551338-19 2018 Sirolimus expanded CD4+CD25+FoxP3+ regulatory T cells and CD8+ memory T-cell populations and inhibited interleukin-4 and interleukin-17 production by CD4+ and CD4-CD8- double-negative T cells after 12 months. Sirolimus 0-9 CD8a molecule Homo sapiens 163-166 29445370-4 2017 Robustly expanded CD8+ Tregs displayed a specific gene signature, upregulated cytokines and expansion in the presence of rapamycin greatly improved proliferation and suppression. Sirolimus 121-130 CD8a molecule Homo sapiens 18-21 25833958-9 2015 As co-administering Flt3L, rapamycin, and antigen blocked CD8(+) T-cell and antibody responses in models of gene and protein therapy, we conclude that the differential effect of rapamycin on DC subsets can be exploited for improved tolerance induction. Sirolimus 27-36 CD8a molecule Homo sapiens 58-61 26437614-9 2016 Rapamycin treatment increased the frequency of mouse CD8 RSV-M282-90 pentamer-positive T cells and the frequency of RSV-specific memory T cells precursors. Sirolimus 0-9 CD8a molecule Homo sapiens 53-56 26680373-10 2016 After transplantation with CB and rapamycin, donor-reactive Eomes(lo)CTLA4(hi) CD8+ T cells were reduced. Sirolimus 34-43 CD8a molecule Homo sapiens 79-82 26037126-7 2015 Treatment with rapamycin increased survival, blocked breakdown of the blood-brain barrier and brain hemorrhaging, decreased the influx of both CD4(+) and CD8(+) T cells into the brain and the accumulation of parasitized red blood cells in the brain. Sirolimus 15-24 CD8a molecule Homo sapiens 154-157 25989700-0 2015 Rapamycin ameliorates the CTLA4-Ig-mediated defect in CD8(+) T cell immunity during gammaherpesvirus infection. Sirolimus 0-9 CD8a molecule Homo sapiens 54-57 25989700-3 2015 Using a murine model of latent viral infection, we observed that rapamycin treatment alone led to a significant increase in virus-specific CD8(+) T cells, as well as increased functionality of these cells, including the ability to make multiple cytokines, while CTLA4-Ig treatment alone significantly dampened the response and inhibited the generation of polyfunctional antigen-specific CD8(+) T cells. Sirolimus 65-74 CD8a molecule Homo sapiens 139-142 25989700-3 2015 Using a murine model of latent viral infection, we observed that rapamycin treatment alone led to a significant increase in virus-specific CD8(+) T cells, as well as increased functionality of these cells, including the ability to make multiple cytokines, while CTLA4-Ig treatment alone significantly dampened the response and inhibited the generation of polyfunctional antigen-specific CD8(+) T cells. Sirolimus 65-74 CD8a molecule Homo sapiens 387-390 25989700-4 2015 However, the addition of rapamycin to the CTLA4-Ig regimen was able to quantitatively and qualitatively restore the antigen-specific CD8(+) T cell response to the virus. Sirolimus 25-34 CD8a molecule Homo sapiens 133-136 26122844-6 2015 In animals vaccinated with CyaA-E7, rapamycin administration completely abolished recruitment of CD8+ T cells into TC-1 tumors along with the ability of the vaccine to reduce infiltration of T regulatory cells and myeloid-derived suppressor cells. Sirolimus 36-45 CD8a molecule Homo sapiens 97-100 24913978-4 2014 We found that functional CD8 T cell and macrophage responses to both viral and intracellular bacterial pathogens were depressed in mice in vivo and in humans to phorbol ester and calcium ionophore stimulation in vitro in the face of low-dose Rapa treatment. Sirolimus 242-246 CD8a molecule Homo sapiens 25-28 25070853-3 2014 The mechanisms and signals that control the formation of tissue-resident memory CD8 T cells are poorly understood; however, one key regulator of memory CD8 T cell differentiation, mammalian target of rapamycin kinase, can be inhibited by rapamycin. Sirolimus 200-209 CD8a molecule Homo sapiens 80-83 25070853-3 2014 The mechanisms and signals that control the formation of tissue-resident memory CD8 T cells are poorly understood; however, one key regulator of memory CD8 T cell differentiation, mammalian target of rapamycin kinase, can be inhibited by rapamycin. Sirolimus 200-209 CD8a molecule Homo sapiens 152-155 22300641-3 2012 Both unpulsed and sirolimus-pulsed Tregs (SPTs) are capable of inhibiting proliferation of multiple T cell subpopulations, including CD4(+) and CD8(+) T cells, as well as antigen-experienced CD28(+) CD95(+) memory and CD28(-) CD95(+) effector subpopulations. Sirolimus 18-27 CD8a molecule Homo sapiens 145-148 24683191-7 2014 DN T cells had greater IL-4 expression than CD4(+) or CD8(+) T cells of SLE patients after 3-d in vitro stimulation, which was suppressed by rapamycin (control: 9.26 +- 1.48%, rapamycin: 5.03 +- 0.66%; p < 0.001). Sirolimus 141-150 CD8a molecule Homo sapiens 54-57 24107844-6 2014 The number of circulating CD4(+)/CD25(high)/Foxp3(+)/CTLA4(+) Tregs, CD8(+)CD28(-) T cells, and HLA-G serum levels were higher in the rapamycin-treated group. Sirolimus 134-143 CD8a molecule Homo sapiens 69-72 24107844-9 2014 Thus, rapamycin induces the upregulation of ILT3 and ILT4 on the DC surface, and this effect is associated with an increase in the number of Tregs and expansion of the CD8(+)CD28(-) T cell population. Sirolimus 6-15 CD8a molecule Homo sapiens 168-171 24123683-7 2013 However, the concurrent administration of rapamycin, with or without IL-2/anti-IL-2 Ab complexes, to the transplant recipients significantly improved Foxp3 stability in CD4 iTregs (and, to a lesser extent, CD8 iTregs), such that they remained detectable 12 wk after transfer. Sirolimus 42-51 CD8a molecule Homo sapiens 206-209 23799424-0 2013 Expansion of memory-type CD8+ T cells correlates with the failure of early immunosuppression withdrawal after cadaver liver transplantation using high-dose ATG induction and rapamycin. Sirolimus 174-183 CD8a molecule Homo sapiens 25-28 21511183-5 2011 The ability of rapamycin to augment HP-induced memory was cell-intrinsic given that silencing mTOR in CD8+ T cells generated identical outcomes. Sirolimus 15-24 CD8a molecule Homo sapiens 102-105 22379028-4 2012 Strikingly, a short course of high-dose, but not low-dose, rapamycin treatment transiently blocks viral vaccination-induced mammalian target of rapamycin activity in CD8(+) T cells favoring persistence and Ag-recall responses over type 1 effector maturation; however, prolonged high-dose rapamycin administration abrogated memory responses. Sirolimus 59-68 CD8a molecule Homo sapiens 166-169 22379028-6 2012 These results demonstrate the impact a regimen of rapamycin treatment has on vaccine-induced CD8(+) T cell responses and indicates that judicious application of rapamycin can augment vaccine efficacy for chronic challenges. Sirolimus 50-59 CD8a molecule Homo sapiens 93-96 22186790-3 2012 Vaccination in combination with both rapamycin (to modulate differentiation) and an OX40 agonist (to enhance costimulation) increased both the quantity and polyfunctionality of the CD8(+) memory T cell population, with expansion of the T(EM) and memory precursor populations. Sirolimus 37-46 CD8a molecule Homo sapiens 181-184 21611151-4 2011 RESULTS: Antigen-activated CD8(+) T cells treated with rapamycin gave rise to 5-fold more long-lived memory T cells in vivo than untreated control T cells. Sirolimus 55-64 CD8a molecule Homo sapiens 27-30 21439133-0 2011 Rapamycin generates graft-homing murine suppressor CD8(+) T cells that confer donor-specific graft protection. Sirolimus 0-9 CD8a molecule Homo sapiens 51-54 21439133-3 2011 In this study, we investigated the ability of short-term RPM treatment in promoting long-term acceptance (LTA) of MHC-mismatched skin allografts by generating a CD8(+) suppressor T-cell population. Sirolimus 57-60 CD8a molecule Homo sapiens 161-164 21439133-10 2011 Our data supported the notion that RPM-induced suppressor CD8(+) T cells home to the allograft and exert donor-specific graft protection. Sirolimus 35-38 CD8a molecule Homo sapiens 58-61 20933441-5 2010 DC-specific Pten targeting in vivo caused the expansion of CD8(+) and CD103(+) cDC numbers, which was reversible by rapamycin. Sirolimus 116-125 CD8a molecule Homo sapiens 59-62 16477233-9 2006 Next to lowering precursor frequencies, rapamycin also inhibited T cell expansion by inducing apoptosis in divided alloreactive CD4+ and CD8+ T cells. Sirolimus 40-49 CD8a molecule Homo sapiens 137-140 16461044-5 2006 The percentages of CD8+ and CD4+ effector memory T cells, as defined by the CD3+CD45RO+CD27- phenotype, were significantly reduced in patients who received a sirolimus-eluting stent compared with the basal values. Sirolimus 158-167 CD8a molecule Homo sapiens 19-22 19424019-8 2009 In conclusion, lymphopenia-induced IL-7 production after induction with ATG and sirolimus might lead to emergence of IFN-gamma-secreting CD8+ T-cells responsible for acute rejection after immunosuppression withdrawal. Sirolimus 80-89 CD8a molecule Homo sapiens 137-140 15585311-6 2005 We found that the number of CD8+ T(EM), as defined by CD3+CD45R0+CD8+CD27- phenotype, was significantly reduced in patients receiving a rapamycin-eluting stent as compared with basal values. Sirolimus 136-145 CD8a molecule Homo sapiens 28-31 15585311-6 2005 We found that the number of CD8+ T(EM), as defined by CD3+CD45R0+CD8+CD27- phenotype, was significantly reduced in patients receiving a rapamycin-eluting stent as compared with basal values. Sirolimus 136-145 CD8a molecule Homo sapiens 65-68 15585311-9 2005 These findings suggest that rapamycin eluted from medicated coronary stents rapidly induce a redistribution of memory CD8+ T lymphocyte subsets, with a significant decrease of T(EM) and a corresponding increase of T(CM) increase circulating within the coronary sinus. Sirolimus 28-37 CD8a molecule Homo sapiens 118-121 8286755-7 1994 In these studies, we showed that RAPA administration can inhibit MHC class I-restricted CD8+ or class II-restricted CD4+ T-cell-mediated graft rejection without compromising recipient survival. Sirolimus 33-37 CD8a molecule Homo sapiens 88-91 7586731-0 1995 Direct inhibition of human CD8+ lymphocyte activation by cyclosporine A and Rapamune-Sirolimus. Sirolimus 76-84 CD8a molecule Homo sapiens 27-30 7586731-0 1995 Direct inhibition of human CD8+ lymphocyte activation by cyclosporine A and Rapamune-Sirolimus. Sirolimus 85-94 CD8a molecule Homo sapiens 27-30 7586731-1 1995 Cyclosporin A (CsA) and Rapamune-Sirolimus (RAP) have been shown to inhibit the in vitro activation of heterogeneous lymphocytes populations, but little is known about their direct actions on isolated CD8+ lymphocytes. Sirolimus 24-32 CD8a molecule Homo sapiens 201-204 14573608-4 2004 Previously, we found that, depending on the strength of the signal delivered to the T cell via both the T cell receptor and the costimulatory molecule CD28, CD8+ T cells are capable of rapamycin-resistant proliferation. Sirolimus 185-194 CD8a molecule Homo sapiens 157-160 11207273-5 2001 Surprisingly, a heterogeneous proliferative response in the presence of rapamycin was observed among different Ag-specific CD8(+) T cell clones; this was also observed in CD8(+) peripheral blood T cells activated with TCR cross-linking ex vivo. Sirolimus 72-81 CD8a molecule Homo sapiens 123-126 11207273-5 2001 Surprisingly, a heterogeneous proliferative response in the presence of rapamycin was observed among different Ag-specific CD8(+) T cell clones; this was also observed in CD8(+) peripheral blood T cells activated with TCR cross-linking ex vivo. Sirolimus 72-81 CD8a molecule Homo sapiens 171-174 11207273-8 2001 Moreover, rapamycin-resistant proliferation of the CD8(+) T cell clones was blocked by anti-IL-2 Abs, suggesting that while some of the parallel pathways triggered by IL-2R signaling are sensitive to the effects of rapamycin, others account for the Ag-driven rapamycin resistance. Sirolimus 10-19 CD8a molecule Homo sapiens 51-54 11207273-8 2001 Moreover, rapamycin-resistant proliferation of the CD8(+) T cell clones was blocked by anti-IL-2 Abs, suggesting that while some of the parallel pathways triggered by IL-2R signaling are sensitive to the effects of rapamycin, others account for the Ag-driven rapamycin resistance. Sirolimus 215-224 CD8a molecule Homo sapiens 51-54 35235777-6 2022 Rather, loss of Slc6a8 or Ckb disrupts naive T cell homeostasis and weakens TCR-mediated activation of mechanistic target of rapamycin complex 1 (mTORC1) signaling required for CD8+ T cell expansion. Sirolimus 125-134 CD8a molecule Homo sapiens 177-180