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T细胞是肺移植术后免疫应答的主要效应细胞,其细胞亚群水平对肺移植受者机体免疫状态具有重要影响。本文综述CD4+ T细胞、CD8+ T细胞和调节性T细胞的免疫学机制及其与肺移植术后原发性移植肺功能障碍、排斥反应、免疫耐受和感染等的关系,同时探讨监测肺移植术后T细胞亚群的临床意义。 相似文献
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BACKGROUND: Based on their chemoattractant properties, it is likely that chemokines play a role in recruiting alloantigen-primed T cells to allografts and in amplifying inflammation within the graft. The graft-infiltrating leukocytes producing specific chemokines remain largely unknown. METHODS: We tested the intragraft RNA expression of the chemokine RANTES (regulated on activation normal T expressed and secreted) and granzyme B during rejection of full thickness, allogeneic skin grafts by C57BL/6 mice. Grafts with different immunogenetic disparities were chosen to test expression when rejection was mediated by CD4+, CD8+, or both CD4+ and CD8+ T cells. RNA expression was also tested in purified CD4+ and CD8+ T cell populations from skin graft recipients. Immunohistology was performed on graft sections to test colocalization of RANTES protein and graft-infiltrating CD4+ and CD8+ T cells. RESULTS: Intra-allograft RANTES RNA expression was not observed during CD4+ T cell-mediated rejection. Expression of RANTES and granzyme B RNA was observed at low levels in purified populations of CD8+, but not CD4+, T cells from the spleen and lymph nodes of graft recipients beginning at day 7 after transplantation and increased thereafter. Intra-allograft RANTES protein was associated with a small number of graft-infiltrating CD8+ T cells but was also associated with endothelial cells and with many graft-infiltrating CD4+ T cells. CONCLUSIONS: CD8+ T cells produce RANTES during allogeneic skin graft rejection. In the allograft, the chemokine also colocalizes with CD4+ T cells that do not produce RANTES. 相似文献
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目的 探讨他克莫司(FK506)对肝移植受者外周血T淋巴细胞亚群及其表面共刺激分子表达的影响。方法 采用荧光标记单克隆抗体和流式细胞技术,测定术后采用FK506治疗的肝移植受者(FK506治疗组)在用FK506后1、2、3、4周时的外周血T淋巴细胞亚群及其表面共刺激分子CD28、CD152和ICOS分子的表达情况,以健康志愿者(健康对照组)和患终末期肝脏疾病拟行肝移植者(肝病对照组)为对照。结果 CD3^+T淋巴细胞在各组间的差异均无统计学意义(P〉0.05)。经FK506治疗后,肝移植患者的CD4^+T淋巴细胞逐渐减少,CD8^+T淋巴细胞逐渐增加,并恢复至健康对照组水平(P〉0.05)。FK506治疗组T淋巴细胞亚群表面CD28分子和ICOS分子表达逐渐下降,并明显低于健康对照组(P〈0.05),而CD152分子表达增加,且明显高于健康对照组(P〈0.05);其ICOS分子表达水平的下降晚于CD28分子,CD4^+CD28^+T淋巴细胞、CD8^+CD28^+T淋巴细胞和CD4^+ICOS^+T淋巴细胞均呈现相近的变化规律。结论 FK506能迅速纠正移植受者T淋巴细胞亚群紊乱,并抑制正性共刺激分子CD28和ICOS的表达,促进负性共刺激分子CD152的表达。 相似文献
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Rejection in lung transplantation--an immunohistochemical study of transbronchial biopsies. 总被引:2,自引:0,他引:2
J de Blic M Peuchmaur F Carnot C Danel M Deruesne P Reynaud P Scheinmann N Brousse 《Transplantation》1992,54(4):639-644
The number, distribution, and phenotype of mononuclear cells infiltrating the allograft lung transplant were determined immunohistochemically with monoclonal antibodies directed against cellular antigens (CD3, CD4, CD8, CD22, CD25, CD16, CD56, CD68, HLA-DR) on frozen sections of transbronchial biopsies. Seventy-two transbronchial biopsies from 21 patients undergoing lung or heart-lung transplantation were evaluated histologically and immunohistologically in a prospective study. Four major results were obtained in the graft lung parenchyma: (1) whatever the histological grading of rejection, T lymphocytes expressing CD3 were present and in a significantly higher number than in control subjects (P < 0.0005); (2) there was a positive correlation between histological rejection and the number of CD3+, CD8+, CD25+, CD16+ cells (P < 0.01); (3) the CD4/CD8 ratio was inverted (0.52 +/- 0.04), with no correlation with the histological rejection; and (4) the number and location of CD3+, CD25+ cells did not correlate with CMV identification in bronchoalveolar lavage. Immunohistochemical criteria could be used for diagnosis of rejection in the management of heart-lung transplantation. 相似文献
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CD69 expression on peripheral CD8 T cells correlates with acute rejection in renal transplant recipients 总被引:6,自引:0,他引:6
BACKGROUND: The development of a noninvasive method to diagnose renal allograft rejection could prevent the complications associated with graft biopsy and allow more accurate surveillance of allograft function. The present study determines whether expression of CD69 on peripheral T lymphocytes of renal allograft recipients correlates with the presence of acute graft rejection. METHODS: Peripheral blood T lymphocytes from healthy volunteers, renal allograft recipients with elevated creatinine but no evidence of rejection on biopsy, and renal allograft recipients with biopsy-proven rejection were analyzed by flow cytometry for the expression of CD69 and various intracellular cytokines (interleukin-2, interferon-gamma). Results were then compared with the degree of rejection on biopsy. RESULTS: CD69 expression on CD3+, CD4+, and CD8+ T-cell subsets was low in controls and transplant recipients without allograft rejection. In contrast, patients with renal allograft rejection showed significantly elevated percentages of CD69+ cells in the CD3+ (P<0.01) and CD8+ subsets (P<0.01). The fraction of CD69+ and CD8+ T cells was found to be a more clinically useful test based on receiver-operator characteristics. CD69 expression on CD4+ T cells did not correlate with rejection. Significant intracellular cytokine levels were not detected in unstimulated T cells from any of the groups; stimulation with mitogens increased expression equally among the three groups. CONCLUSIONS: We demonstrate that expression of CD69 on CD3+ and CD8+ peripheral blood T cells correlates closely with the presence of acute graft rejection in renal allograft recipients. Measurement of this surface marker may provide a rapid, noninvasive, and accurate means by which graft rejection can be identified. 相似文献
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Volker Daniel Cord Naujokat Mahmoud Sadeghi Rolf Weimer Fabrice Renner Sevgi Yildiz Gerhard Opelz 《Transplant international》2008,21(7):646-660
There is evidence that interferon-gamma (IFN-gamma)-dependent interactions of dendritic cell (DC), T regulatory (Treg), and T suppressor (Ts) subpopulations contribute to allograft acceptance. We measured DC subsets, CD3+CD4+CD25+ (Treg phenotype) and CD3+CD8+CD28(-) (Ts phenotype) peripheral blood lymphocytes (PBL) expressing Foxp3, Th1 or Th2 cytokines, peripheral T- and B-cell counts, and plasma cytokines in 33 kidney transplant recipients with a serum creatinine of < or =1.8 mg/dl and 32 recipients with a serum creatinine of > or =2.0 mg/dl more than 100 days post-transplant. Cell subsets were measured in whole blood using four-color flow cytometry. Patients with increased creatinine had less frequently detectable CD3+CD4+CD25+IFN-gamma+ PBL than patients with good graft function (P = 0.017). In patients with good graft function, CD3+CD4+CD25+IFN-gamma+ PBL were associated with high Foxp3+, IL-2+, IL-12+, IL-4+, and IL-10+ CD3+CD4+CD25+ T PBL (P < 0.001), low CD3+CD8+CD28(-)Foxp3+ (P = 0.002), CD3+CD4+DR+ (P = 0.002), CD3+CD8+DR+ T (P = 0.005) and CD19+ B PBL (P = 0.005), and low lineage(-)HLA-DR+CD11c+CD123(-) DC1 (P = 0.006). Patients with impaired graft function did not show these associations. Additional flow cytometric analysis confirmed strong co-expression of IFN-gamma and Foxp3 by CD4+CD25+ PBL particularly in patients with good graft function. Our data support an immunoregulatory role of CD3+CD4+CD25+Foxp3+IFN-gamma+ cells in a subgroup of transplant recipients with good graft acceptance. 相似文献
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R. A. Nash M. Yunosov K. Abrams B. Hwang C. Castilla-Llorente P. Chen A. S. Farivar G. E. Georges R. C. Hackman W. J. E. Lamm M. Lesnikova H. D. Ochs J. Randolph-Habecker S. F. Ziegler R. Storb B. Storer D. K. Madtes R. Glenny M. S. Mulligan 《American journal of transplantation》2009,9(5):1037-1047
Long-term survival after lung transplantation is limited by acute and chronic graft rejection. Induction of immune tolerance by first establishing mixed hematopoietic chimerism (MC) is a promising strategy to improve outcomes. In a preclinical canine model, stable MC was established in recipients after reduced-intensity conditioning and hematopoietic cell transplantation from a DLA-identical donor. Delayed lung transplantation was performed from the stem cell donor without pharmacological immunosuppression. Lung graft survival without loss of function was prolonged in chimeric (n = 5) vs. nonchimeric (n = 7) recipients (p ≤ 0.05, Fisher's test). There were histological changes consistent with low-grade rejection in 3/5 of the lung grafts in chimeric recipients at ≥1 year. Chimeric recipients after lung transplantation had a normal immune response to a T-dependent antigen. Compared to normal dogs, there were significant increases of CD4+INFγ+, CD4+IL-4+ and CD8+ INFγ+ T-cell subsets in the blood (p < 0.0001 for each of the three T-cell subsets). Markers for regulatory T-cell subsets including foxP3, IL10 and TGFβ were also increased in CD3+ T cells from the blood and peripheral tissues of chimeric recipients after lung transplantation. Establishing MC is immunomodulatory and observed changes were consistent with activation of both the effector and regulatory immune response. 相似文献