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Summary: A cardinal feature of the adaptive immune response is its ability to generate long-lived populations of memory T lymphocytes. Memory T cells are specific to the antigen encountered during the primary immune response and react rapidly and vigorously upon re-encounter with the same antigen. Memory T cells that recognize microbial antigens provide the organism with long-lasting protection against potentially fatal infections. On the other hand, memory T cells that recognize donor alloantigens can jeopardize the survival of life-saving organ transplants. We review here the immunobiology of memory T cells and describe their role in the rejection of solid organ allografts. 相似文献
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Salim A Kanaan Stephen Poole Nayef E Saadé Suhayl Jabbur Bared Safieh-Garabedian 《Journal of neuroimmunology》1998,86(2):496
In the endotoxin-induced inflammation, interleukin-10 reduced significantly, and in a dose-dependent manner, the inflammatory pain as assessed by mechanical and thermal tests. The levels of Tumour Necrosis Factor (TNF)α and NGF were upregulated at 1.5 h whereas those of IL-1β at 6 h after ET injection. IL-10 downregulated the levels of TNFα (from 4974.75±875.78 to 1008±350 pg/hind paw), NGF (from 352.9±46.7 to 33.9±2.4 pg/hind paw) and IL-1β (from 2773.88±423.96 to 1108±399.56 pg/hind paw). These data suggest that IL-10 inhibits ET-induced hyperalgesia by downregulation of TNFα, IL-1β and NGF production. 相似文献
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Hisham Dokainish M.D. John Nguyen M.D. Ranjita Sengupta M.D. Manu Pillai M.D. Mahboob Alam M.D. Jaromir Bobek R.C.I.S. Nasser Lakkis M.D. 《Echocardiography (Mount Kisco, N.Y.)》2010,27(8):946-953
Background: There are few data on echocardiographic indexes incorporating peak mitral inflow velocity (E), left atrial volume index (LAVi), and pulmonary artery pressure (PAP) for estimation of left ventricular (LV) filling pressure in patients with preserved LV ejection fraction (EF ≥ 50%). Methods: Patients underwent echocardiography ≤20 minutes of cardiac catheterization. Echocardiographic variables were compared to invasively measured LV end‐diastolic pressure (LVEDP). Results: Of the 122 patients, 67 (55%) were women, the mean age was 55 ± 9 years, the mean left ventricular ejection fraction (LVEF) was 61 ± 6%, 107 (88%) were hypertensive, and 79 (65%) had significant coronary artery disease at catheterization. E/Ea correlated with LVEDP (R = 0.68, P < 0.0001), compared to PAP (R = 0.53, P < 0.001), peak E velocity (R = 0.48, P < 0.001), and LAVi (R = 0.48, P < 0.001). E/Ea > 12 had 75% sensitivity and 78% specificity for LVEDP ≥ 20 mmHg (area under curve (AUC) = 0.79, P < 0.0001), compared with (PAP + LAVi)/2 > 30 (sensitivity = 72%, specificity = 80%, AUC = 0.84, P < 0.001) and (E + LAVi)/2 > 57 (sensitivity = 73% and specificity = 81%, AUC = 0.82, P < 0.001) (P = NS). E <60 cm/sec had 94% negative, and E>90 cm/sec had 96% positive, predictive value for LVEDP ≥ 20 mmHg. (E + LAVi)/2 added incrementally to E/Ea when E/Ea was in the gray zone. Conclusions: New, simple echocardiographic equations, (E + LAVi)/2 and (PAP + LAVi)/2, have comparable accuracy to E/Ea for LVEDP estimation in patients with cardiac disease and preserved LVEF, and (E + LAVi)/2 added incrementally to E/Ea alone when E/Ea was in the gray zone. Peak E velocity alone had high negative and positive predictive value for elevated LVEDP in this population. These simple echocardiographic variables could be used—in isolation or with E/Ea—in patients with cardiac disease and preserved LVEF for the diagnosis of diastolic heart failure. Echocardiography 2010;27:946‐953) 相似文献
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Interferon-gamma is necessary for initiating the acute rejection of major histocompatibility complex class II-disparate skin allografts. 总被引:3,自引:0,他引:3
G H Ring S Saleem Z Dai A T Hassan B T Konieczny F K Baddoura F G Lakkis 《Transplantation》1999,67(10):1362-1365
BACKGROUND: Although interferon (IFN)gamma has immunostimulatory functions, it is not essential for the acute rejection of fully allogeneic grafts in mice. It is not known whether IFNgamma plays a critical role in the acute rejection of MHC class I- or MHC class II-disparate allografts. METHODS: We studied the survival of skin allografts transplanted from fully allogeneic (BALB/c), MHC class I-disparate (bml), or MHC class II-disparate (bm12) donors to C57BL/6 wild-type (IFNgamma+/+) and IFNgamma gene-knockout (IFNgamma-/-) recipients. We also investigated the in vitro responses of IFNgamma+/+ and IFNgamma-/- T cells to MHC class II-disparate splenocytes. RESULTS: We found that IFNgamma-/- recipients reject BALB/c and bml skin grafts at the same rate as IFNgamma+/+ mice but are not capable of rejecting bm12 skin. Despite the inability of IFNgamma-/- mice to reject bm12 skin grafts, IFNgamma-/- T cells displayed vigorous proliferation and cytotoxic responses when stimulated with bm12 splenocytes in vitro. Furthermore, priming IFNgamma-/- recipients with bm12 splenocytes enabled these mice to reject bm12 skin grafts at a normal rate and to mount a cutaneous delayed-type hypersensitivity response to the bm12 antigen. CONCLUSION: The data demonstrate that IFNgamma is not necessary for generating effector mechanisms associated with acute transplant rejection but that it is required for initiating alloimmune responses to MHC class II-disparate skin grafts. 相似文献
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Diane Mege Gilles Manceau Laura Beyer-Berjot Valérie Bridoux Zaher Lakkis Aurélien Venara Thibault Voron Francesco Brunetti Igor Sielezneff Mehdi Karoui 《European journal of surgical oncology》2018,44(10):1522-1531
Aim
To report the results of surgery for obstructive right colon cancer (ORCC) and to identify risk factors associated with worse outcomes that may help surgeons to choose the best surgical option.Methods
This is a retrospective national cohort study, including all patients operated on for ORCC from 2000 to 2015. Those treated with colonic stent or symptomatic treatment were excluded. We described outcomes after surgery for ORCC and performed multivariate analyses for mortality, morbidity and survival.Results
Among 776 patients analyzed, 716 (92%) had their primary tumor removed, with primary anastomosis in 582 (82%). The remaining 194 underwent anastomosis with loop ileostomy (n = 21), resection with double-end stoma (n = 113), defunctioning stoma without resection (n = 48) and ileocolic by-pass (n = 12). Postoperative mortality, morbidity and anastomotic leak rates were 10%, 51% and 14%, respectively. In multivariate analysis, age >70, ASA score ≥3 and hemodynamic instability were predictors of postoperative mortality whereas ASA score ≥3, hemodynamic instability and intra-operative complications were predictors of severe morbidity. No factors were correlated with anastomotic leak. After a median follow-up of 26 months, 8% of patients were alive with a permanent stoma. Five-year overall, disease-free and cancer-specific survival was 42%, 42% and 62%, respectively. In multivariate analysis, peritonitis, synchronous metastases and absence of adjuvant chemotherapy were predictors of decreased overall survival.Conclusions
Emergency surgery for ORCC is associated with high mortality and morbidity. Two third of patients with ORCC can be managed with resection and primary anastomosis. For high-risk patients, a staged surgical management may be discussed. 相似文献70.
CD4+CD25+ regulatory T cells suppress allograft rejection mediated by memory CD8+ T cells via a CD30-dependent mechanism 总被引:5,自引:0,他引:5 下载免费PDF全文
Dai Z Li Q Wang Y Gao G Diggs LS Tellides G Lakkis FG 《The Journal of clinical investigation》2004,113(2):310-317
CD4(+)CD25(+) regulatory T (Treg) cells suppress naive T cell responses, prevent autoimmunity, and delay allograft rejection. It is not known, however, whether Treg cells suppress allograft rejection mediated by memory T cells, as the latter mount faster and stronger immune responses than their naive counterparts. Here we show that antigen-induced, but not naive, Treg cells suppress allograft rejection mediated by memory CD8(+) T cells. Suppression was allospecific, as Treg cells induced by third-party antigens did not delay allograft rejection. In vivo and in vitro analyses revealed that the apoptosis of allospecific memory CD8(+) T cells is significantly increased in the presence of antigen-induced Treg cells, while their proliferation remains unaffected. Importantly, neither suppression of allograft rejection nor enhanced apoptosis of memory CD8(+) T cells was observed when Treg cells lacked CD30 or when CD30 ligand-CD30 interaction was blocked with anti-CD30 ligand Ab. This study therefore provides direct evidence that pathogenic memory T cells are amenable to suppression in an antigen-specific manner and identifies CD30 as a molecule that is critical for the regulation of memory T cell responses. 相似文献