CD4(+) CD56(+) lineage-negative malignancies are rare tumors of plasmacytoid dendritic cells

CD4(+) CD56(+) lineage-negative malignancies are difficult to diagnose and classify. Recent studies have suggested that these malignancies may derive from plasmacytoid dendritic cells (pDC). In this report, we examine 10 cases of CD4+, CD56+ lineage-negative malignancies that presented in various tissue sites. The goal was to identify the morphologic, immunophenotypic, and genotypic findings to devise a diagnostic approach to tissue biopsies of these lesions and to confirm the proposed cell of origin. The mean age was 66 years (range, 45-80 years) with a male predominance (8 males/2 females). Frequent sites of disease included skin (60%) and peripheral blood/bone marrow (70%). Tumor cells were positive for CD45, CD43, CD4, and CD56 (9 of 10). The pDC markers, CD123 (9 of 10) and CD45RA (10 of 10), were detected by immunoperoxidase staining. Also noted was CD2 positivity (1 case), weak CD7 positivity (4 of 8 cases), weak CD33 (4 of 9 cases), TdT (2 cases), and CD68 (2 cases). All cases were otherwise negative for EBV (EBER), B-cell, T-cell, myeloid, and NK cell markers. T-cell receptor-gamma gene rearrangement was negative in all cases. Complex structural chromosomal abnormalities were seen in 3 of 5 cases, a subset of which may be recurrent in pDC malignancy. Overall prognosis was poor despite multiagent chemotherapy and/or radiation. Our study confirms that CD4+/CD56+ lineage-negative tumors are derived from pDC and have characteristic clinical, histopathologic, and immunophenotypic features. Furthermore, these rare neoplasms can be readily diagnosed using recently developed immunoperoxidase techniques.     

Nasal natural killer cell lymphoma in a post-renal transplant patient

Posttransplant lymphoproliferative disorders in organ allograft recipients are most commonly of B-cell origin and only occasionally of T-cell origin. We present here a case of nasal natural killer cell lymphoma associated with Epstein-Barr virus that occurred in a recipient of a renal transplant 4 years posttransplantation. Immunohistochemically, the lymphoma cells showed CD2-, surface CD3-, cytoplasmic CD3E+, CD56+, CD57-, CD16-, and CD43+ phenotype. Analyses of T-cell receptor beta and gamma genes showed germ line configurations. EBER-1 was detectable in the lymphoma cells. The patient was diagnosed as having natural killer cell lymphoma and was treated with six courses of combination chemotherapy for non-Hodgkin's lymphoma He has been in remission for more than 3 years thereafter. To the best of our knowledge, this is the first report of a posttransplant NK cell lymphoma associated with Epstein-Barr virus.     

Clonal T-cell populations and increased risk for cytotoxic T-cell lymphomas in B-CLL patients: clinicopathologic observations and molecular analysis

Chronic lymphocytic leukemia (CLL) is associated with increased risk of malignancy, but the occurrence of other lymphomas, in particular T-cell lymphomas, is rare. We identified 7 cases of peripheral T-cell malignancy associated with B-cell-derived CLL from the files of two institutions over a 20-year period. The presence of both B and T lymphoproliferative disorders was confirmed in all cases by immunophenotype and in 6 cases by gene rearrangements. Six patients developed peripheral T-cell lymphoma (PTCL), unspecified, during the course of CLL (10-168 months). In all 5 evaluable cases, the cells had a cytotoxic T-cell phenotype; the sixth case was CD56+, but TIA-1 and Granzyme B could not be studied. A seventh patient with CLL developed mycosis fungoides, and an aggressive NK cell leukemia. To investigate possible risk factors for the development of PTCL, we screened 100 unselected peripheral blood samples from newly diagnosed CLL patients by PCR for the presence of clonal T cell populations. We found evidence of clonal T-cell expansion in 8 patients and increased lymphocytes with large granular lymphocyte morphology in 7 of 8 cases. The immunophenotype was assessed by multicolor flow cytometry and in 4 cases the T-cell expansion was composed of either CD3+/CD8+ or CD3+/CD4-/CD8- cells. The cytotoxic nature of the clonal T-cell expansions in the peripheral blood correlates with the cytotoxic nature of the PTCLs, but their role in the subsequent development of T-cell lymphomas is still unclear. PTCL following CLL should be distinguished from typical Richter syndrome, which it can mimic clinically.     

Expression of CD158b on peripheral blood lymphocytic cell after kidney transplantation

OBJECTIVE: To investigate the expression of CD158b on peripheral blood lymphocytes after kidney transplantation. METHODS: Sixty two kidney transplant patients were divided into two groups (normal group and rejection group) according to pathologic results and clinical situation. Blood samples were assessed for percentage of CD3+; CD19+; CD3-CD16/56+; CD3+CD158b+; CD19+CD158b+, and CD3-CD16/56+CD158b+ subsets. RESULTS: The percentages of CD3+ cells preop as well as at 1 and 7 postoperative and the day acute rejection happened were 60.06 +/- 4.67, 40.43 +/- 4.11, 31.67 +/- 4.04, and 39.21 +/- 5.20, respectively. The percentages of CD3-CD16/56+ were 21.65 +/- 1.79, 33.84 +/- 5.45, 38.10 +/- 4.86, and 39.53 +/- 4.80, respectively. The percentages of CD3+CD158b+ were 1.46 +/- 0.31, 1.88 +/- 0.70, 2.03 +/- 1.04, and 0.65 +/- 0.12, respectively. The percentages of CD3-CD16/56+CD158b+ were 5.87 +/- 1.24, 3.57 +/- 0.57, 2.82 +/- 0.45, and 1.60 +/- 0.33, respectively. CONCLUSIONS: The percentage of CD3+ cells in the normal and the rejection groups decreased significantly. The percentages of CD158b+T cells decreased significantly after acute rejection. The percentage of CD158b+NK cells decreased significantly after kidney transplantation, decreasing gradually after acute rejection. The percentage of CD158b+ total T cells decreased significantly following acute rejection. The percentage of CD3-CD16/56+CD158b+ of total NK cells decreased significantly after kidney transplantation and after acute rejection. Because few factors interfere with the expression of CD158b on NK cells, monitoring of this marker may be accurate and sensitive.     

Characterization of an expanded large granular lymphocyte subset lacking natural killer activity present in renal allograft recipients

We have previously reported that, in long-term renal allograft recipients who receive chronic chemical immunosuppression and who are at risk for late chronic viral infections and virus associated tumors, the percentage of lymphocytes the phenotype of which is Leu-7+/Leu-11(-) (CD16) is markedly and significantly increased compared with that in normal controls. Since this population may lack natural killer (NK) activity and may explain the state of decreased host resistance, we carried out studies in 16 kidney transplant recipients on conventional immunosuppression and 10 age-matched normal controls to further define the phenotype, the morphology, and the NK cell activity of this particular subset. Using two-color flow cytometry analysis we found that the Leu-7+ cell subset comprises two essentially nonoverlapping subpopulations, depending on whether cells are coexpressing the NK cell marker Leu-11/CD16 (Leu-7+/Leu-11+ phenotype) or the pan-T cell marker Leu-4/CD3 (Leu-7+/Leu-4+ phenotype). We thus demonstrated that Leu-7+/Leu-11- cells do coexpress the Leu-4+/CD3 surface determinant. The percentage of Leu-7+/Leu-4+ (CD3) is significantly elevated in transplant recipients compared with that in normal controls (26 +/- 4% versus 8 +/- 2%, P less than 0.005). In contrast, the size of the Leu-7+/Leu-11+ cell subset is similar in both groups. Although in transplant recipients 70% of Leu-7+ cells coexpress Leu-4/CD3, only 43% do so in the control group. Cell sorter experiments isolated the Leu-7+/Leu-4+ cells and showed that morphologically these cells are typical large granular lymphocytes that cannot be distinguished from Leu-11+ NK cells. NK-sensitive K562 target cells showed no cytotoxicity. In contrast, Leu-7+/Leu-11+ cells exhibited high killing activity. Therefore, in long-term stable renal allograft recipients at increased risk of developing cancers and chronic viral infections, a subpopulation of non-NK large granular lymphocytes, the phenotype of which is Leu-7+/Leu-11-/Leu-4+, is abnormally expanded. This subset likely contributes to the diminished functional attributes of the chronic drug-induced immunodeficiency.     

胃癌外周血淋巴细胞亚群表达水平对患者生存率的影响

目的探讨胃癌患者外周血淋巴细胞亚群表达与生存率的关系。方法用流式细胞仪检测833例胃癌首诊患者外周血的淋巴细胞亚群CD3^＋、CD4^＋、CD8^＋、CD4^＋／CD8^＋、CD19^＋、CD25^＋、CD44^＋及NK^＋细胞．并根据96名健康对照者的平均检测值分为高表达组和低表达组．比较各亚群高表达组与低表达组患者的生存率。结果与健康对照者相比．胃癌患者CD3^＋、CD8^＋低表达。而CD4^＋,CDl9^＋,CD25^＋、CD4^＋／CD8^＋、CD44^＋,NK^＋高表达（P〈0．05）。CD19^＋高表达与低表达者分别为444例和389例,3年生存率为36．4％和18．5％,差异有统计学意义（P〈0．05）：而其他7种淋巴细胞亚群表达水平则与患者生存率无关（均P〉0．05）。结论与健康人群相比,胃癌患者外周血淋巴细胞亚群发生显著变化．其中CDl9^＋高表达患者具有明显的生存优势。     

Prethymic adult lymphoblastic lymphoma. A clinicopathologic and immunohistochemical analysis.

The clinical, histologic, and immunohistologic features of three cases of pre-T-cell (CD7+/CD2-) lymphoblastic lymphoma in adults are reported. The patients were adults over age 50 years who had a relatively indolent nodal disease, partial involvement of lymph nodes, and primitive immunophenotype. The phenotype of the three cases was TdT+, HLA-DR+, CD34+, CD71+, CD38+, and CD7+, most resembling the normal prothymocyte, and in contrast to normal thymocytes, which generally coexpress CD1+, CD4+, and CD8+. The prethymic T-cell character was further supported by germline T-cell receptor beta and gamma chain genes. In contrast to most reported cases with this early immunophenotype, these patients had nodal disease but not peripheral blood involvement. Two of the three cases were associated with Langerhans' cell histiocytosis (histiocytosis X), a previously unreported association. Because of the Langerhans' cell histiocytosis and the relatively indolent clinical presentation, the differential diagnosis in all cases included both a benign process and a lower-grade lymphoma. Recognition of this unusual form of adult lymphoblastic lymphoma is essential for correct diagnosis and treatment.     

Ex vivo lymphocyte proliferative function is severely inhibited in renal transplant patients on mycophenolate mofetil treatment

Mycophenolate mofetil (MMF) is a recently introduced immunosuppressive drug. Its active form is mycophenolic acid (MPA). MPA specifically inhibits de novo purine synthesis, which is vital for T and B lymphocyte proliferation. We measured lymphocyte subset numbers and mitogen induced proliferation in kidney transplant recipients on different combinations of MMF, cyclosporin A (C), azathioprine (A) and prednisolone (P) (C+A n=70; C+A+P n=15; C+MMF n=45; C+MMF+P n=37) and normals (n=73). Patients on MMF had severely reduced phytohaemagglutinin A (PHA) induced proliferation compared to normals (Nml 2766+/-926 CPM/1000 lymphocytes [mean+/-S.D.]; C+MMF 282+/-406; C+MMF+P 195+/-496); non-MMF patients did not differ from normal. Similar inhibition of Poke Weed Mitogen and Staphylococcal enterotoxin B induced proliferation was observed. Cell cycle studies established that MMF patients had a significantly higher proportion of lymphocytes in the G0/G1 phase following PHA stimulation than the non-MMF patients. All transplant groups had significantly lower B cell numbers than the normal controls but no differences in CD4 and CD8 T cell numbers. All but the C+MMF group had significantly lower CD16+NK cell numbers than normal, while only the non-MMF groups had significantly lower CD56+NK cell numbers. The proliferation assay used was an ex vivo diluted whole blood technique. Removal of residual MPA by washing the plasma out prior to mitogen stimulation led to a significant increase in proliferation in six out of seven cases. In summary we have found that MMF treatment has a strikingly inhibitory effect on patient ex vivo lymphocyte mitogenic function.     

腹腔化疗对老年结直肠癌病人手术后细胞免疫功能的影响

目的：探讨老年结直肠癌病人手术后腹腔化疗对免疫状况的影响。方法：对1998年1月至2002年12月60岁以上行根治性手术的52例结直肠癌病人进行腹腔化疗前后细胞免疫检测，并将之与我院同期健康老年对照组和行静脉化疗病例进行比较。所有病人于化疗前1d和化疗后1周早晨空腹时静脉采血，测定血清中NK细胞和T细胞亚群。结果：老年结直肠癌病人手术后CD4^＋和NK细胞水平明显低于健康老年人群；老年结直肠癌病人化疗后CD4^＋、CD4^＋／CD8^＋和NK细胞水平低于化疗前，其中静脉化疗病人化疗后较化疗前明显降低，存在统计学意义（P〈0．05）；而腹腔化疗组病人化疗前后上述指标的变化不大，无统计学意义（P〉0．05）。结论：针对老年病人的免疫特点，采用细胞免疫抑制较轻的腹腔化疗方式进行化疗，对老年结直肠癌病人有一定的临床价值。     

曲马多对胃肠道肿瘤患者术中免疫功能的影响

目的 观察曲马多对胃肠道肿瘤患者术中T淋巴细胞亚群和NK细胞数量的影响.方法 30例胃肠道肿瘤行根治手术的患者随机均分为观察组和对照组.观察组麻醉前肌注曲马多1 mg/kg,对照组不使用.于麻醉前、手术1 h和术毕抽取外周静脉血,用流式细胞仪检测T淋巴细胞亚群(CD3+、CD3+CD4+、CD3+CD8+)、活化T细胞(CD3+HLA-DR+)和自然杀伤(NK)细胞(CD3-CDl6+CD56+)数量的变化.结果 两组手术1 h CD3+、CD3+CD4+、CD3+CD4+、CD3+CD8+、CD3+HLA-DR+和NK细胞数量均较麻醉前明显下降,对照组明显低于观察组(P＜0.05);术毕两组各指标有所回升,但对照组仍明显低于麻醉前水平和观察组(P＜0.05).结论 曲马多可减轻胃肠道肿瘤患者术中T淋巴亚群和NK细胞下降的程度,明显改善机体细胞免疫功能的抑制.     

Subcutaneous, blastic natural killer (NK), NK/T-cell, and other cytotoxic lymphomas of the skin: a morphologic, immunophenotypic, and molecular study of 50 patients

A new group of subcutaneous, natural killer (NK), NK/T-cell, and other cytotoxic T-cell lymphomas of the skin has been recently described, and some have been included as distinct clinicopathologic entities in the classification of hematologic malignancies recently proposed by the World Health Organization. In the European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas, they would be classified either as CD30- large T-cell lymphoma, small/medium pleomorphic T-cell lymphoma, or subcutaneous T-cell lymphoma. Precise clinicopathologic and prognostic features of all of them have not yet been well characterized. We studied retrospectively 81 biopsies from 50 patients with subcutaneous, blastic natural killer (NK), NK/T-cell, or other non-mycosis fungoides cytotoxic T-cell lymphomas of the skin. Clinical, morphologic, phenotypical, and genetic features and data on Epstein-Barr virus association allowed us to classify our cases according to the following 7 categories: a) subcutaneous "panniculitis-like" T-cell lymphoma (SPTCL): 10 cases (estimated 5-year survival: 80%); b) blastic NK-cell lymphoma: 12 cases (estimated 5-year survival: 0%); c) nasal-type extranodal NK/T-cell lymphoma: 5 patients (estimated 5-year survival: 0%); d) epidermotropic CD8+ T-cell lymphoma: 5 cases (estimated 5-year survival: 0%); e) cutaneous gamma/delta T-cell lymphoma: 8 cases (estimated 5-year survival: 0%); f) cutaneous alpha/beta pleomorphic T-cell lymphoma: 8 cases (estimated 5-year survival: 0%); and g) cutaneous medium/large pleomorphic T-cell lymphoma, not otherwise specified: 2 cases. Our study shows that these cutaneous lymphomas can be classified according to precise diagnostic categories. With the exception of SPTCL, analysis of follow-up data from our patients showed that these groups of lymphomas are characterized by an aggressive course, regardless of the diagnostic category.     

Lymphocytes subsets in the course of continuous ambulatory peritoneal dialysis (CAPD)

BACKGROUND: We studied lymphocyte subset counts in comparison with normal subjects in order to clarify the abnormalities of cellular immune responses in uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD). METHODS: The study included 37 CAPD patients and 45 normal individuals, as the control group. For the study, CAPD patients were divided into four groups depending on duration of replacement therapy. Group I consisted of patients treated for 0-6 months (n=6), group II for 6-12 months (n=6), group III for 13-24 months (n=16), and group IV for more than 25 months (n=9). Flow cytometry was used for estimation of lymphocyte subsets (determination of CD2, CD3, CD3+/CD4+, CD3+/CD8+, CD3-/16+56+, CD19, CD4/CD8). RESULTS: Our patients started CAPD with decreased lymphocyte subset counts, slightly above the normal range (excluding CD3 -/16+56+, CD2). After 6 months of CAPD therapy, an increase in CD4/CD8 ratio was observed and all examined lymphocyte subset counts decreased (excluding CD2). In patients on CAPD for more than 25 months, CD3+/CD4+, CD19 counts were below the normal range, CD3 -/16+56+ exceeded the upper limit of normal range and at the same time mean total lymphocyte count (TLC) was maintained in the normal range. CONCLUSIONS: We recommend lymphocyte subset determinations for detection of immune abnormalities in the course of CAPD treatment.     

Rejection responses to allogeneic hepatocytes by reconstituted SCID mice, CD4, KO, and CD8 KO mice

INTRODUCTION: The purpose of the current study was to investigate the capacity of CD4+, CD8+, or non-T cells to independently initiate acute rejection of allogeneic hepatocytes using reconstituted SCID, CD4 or CD8 knockout (KO) recipient mice. METHODS: Allogeneic hepatocytes (FVB/N, H-2q) were transplanted into C57BL/6.SCID (H-2b), CD4 KO (H-2b), CD8 KO (H-2b), or beige/beige (H-2b) mice. SCID mice with functioning hepatocellular allografts subsequently received purified non-T cells (NTC), CD4+, or CD8+ splenocytes. Some mice were treated with anti-CD4, anti-CD8, and/or anti-nkl.1 mAb. Recipient mice were also assessed for donor-reactive delayed-type hypersensitivity (DTH) responses and donor-reactive alloantibody production. RESULTS: Median hepatocellular allograft survival time (MST) was 28 days in CD4+ reconstituted SCID mice and 14 days in CD8+ reconstituted SCID mice. SCID hosts reconstituted with NTC demonstrated indefinite hepatocellular allograft survival (>120 days). MST was 10 days in untreated beige/beige (NK cell deficient) mice. MST was 14 days in untreated, 35 days in anti-CD4 mAb treated, and 10 days in anti-nkl.1 mAb treated CD8 KO mice. MST was 10 days in untreated, 35 days in anti-CD8 mAb treated, and 7 days in anti-nk1.1 mAb treated CD4 KO mice. Donor-reactive DTH responses were not detected in reconstituted SCID mice, were minimal in CD4 KO mice, and were prominent in CD8 KO mice after rejection of allogeneic hepatocytes. Similarly, donor-reactive alloantibody, was not detected in CD4 KO hosts, but was readily detected in CD8 KO hosts. CONCLUSIONS: These studies show that both CD4+ and CD8+ T cells (but not host NTC) can independently initiate the rejection of allogeneic hepatocytes. While hepatocyte rejection by isolated CD4+ T cells is not surprising, rejection by CD8+ T cells (in the absence of CD4+ T cells) was unusual, and may explain the failure of "standard" immunosuppressive regimens to suppress acute rejection of allogeneic hepatocytes, as noted in prior studies. Furthermore, NK cells do not appear to be required for either CD4+ T cell or CD8+ T cell initiated hepatocyte rejection.     

肠内营养添加谷氨酰胺对烧伤患者的免疫调理作用

目的 了解烧伤后早期肠内营养添加谷氨酰胺(Gln)对患者免疫调理状态的影响.方法 将24例烧伤患者随机分为2组,每组12例.标准营养(EN)组:给患者喂食标准肠内营养制剂能全力;免疫营养(EIN)组:喂食能全力+Gln.分别于伤后1、4、7、10 d清晨空腹抽血,检测血清总蛋白(TP)、白蛋白(ALB)、前白蛋白(PAB)、转铁蛋白(TF)和免疫球蛋白IgG、IgA、IgM的浓度以及T淋巴细胞亚群CD3+、CD4+、CD8+和CD4+/CD8+的比值.结果 伤后各时相点2组患者TP、ALB、TF、CD3+、IgM组间比较,差异均无统计学意义(P＞0.05).伤后4、7、10 d,EIN组患者PAB浓度分别为(90±14)、(92±16)、(106±21)mg/L,显著高于EN组(60±15)、(64±13)、(72±17)mg/L(P＜0.05).伤后7、10 d,EIN组CD4+细胞百分比为(55±5)%、(56±5)%,明显高于EN组的(45±5)%、(49±5)%(P＜0.05);CD4+/CD8+比值为1.92±0.31和2.36±0.36,明显高于EN组的1.53±0.27和1.72±0.42(P＜0.05);IgA分别为(2.8±0.6)、(3.1±0.6)g/L,IgG为(12.1±1.3)、(14.2±1.3)g/L,显著高于EN组的IgA[(2.2±0.5)、(2.5±0.5)g/L,P＜0.05]和IgG[(9.8±1.2)、(10.4±1.3)g/L,P＜0.05].结论 添加Gln的肠内营养制剂可以促进免疫球蛋白IgA、IgG的合成并增加PAB浓度,改善患者营养状况,纠正免疫功能紊乱.     

Natural Killer-Like T Cell Lymphoma of the Small Intestine: Report of a Case

We report the case of a 77-year-old Japanese man with natural killer (NK)-like T cell lymphoma of the small intestine diagnosed after an emergency laparotomy for perforated peritonitis. Immunohistochemical staining of the tumor showed that the patient had CD3+ CD8+ CD30− CD56+ CD68− CD79a− UCHL-1+ EMA− LMP-1 NK-like T cell lymphoma. The patient had a history of hepatocellular carcinoma (HCC) and was also diagnosed with T cell non-Hodgkin's lymphoma associated with T cell receptor (TCR) reconstruction in the Jγ chain. Intestinal T cell lymphoma is uncommon and very few cases of CD56+ T cell lymphoma, otherwise known as NK-like T cell lymphoma, have been reported. The patient did not have a history of gluten-sensitive enteropathy (celiac disease). Multiple lesions appeared within months after the initial operation and his condition deteriorated rapidly. We think that this patient probably had NK-type granular lymphocyte-proliferative disorder (NK-GLPD) because the percentage of CD16+ CD56+ cells among peripheral blood mononuclear cells was elevated, at 21%. We report this case to help elucidate the relationship between underlying digestive organ disease and the development of intestinal NK-like T cell lymphoma. An accumulation of other such cases is needed to determine the etiology of this disease.     

移植物中不同种类和数量的细胞对异基因外周血造血干细胞移植后急性GVHD的影响

目的 探讨移植物中单个核细胞(MNC),CD34+细胞,T淋巴细胞(包括CD3+、CD3+CD4+、CD3+CD8+和CD4+CD25+),CD3 CD16+CD56+自然杀伤(NK)细胞,以及树突状细胞(DC)Ⅰ和Ⅱ型(DC1和DC2)的数量对人类白细胞抗原(HLA)相合的同胞异基因外周血造血干细胞移植(allo-PBSCT)后急性移植物抗宿主病(aGVHD)的影响.方法 选择65例接受HLA相合的同胞allo-PBSCT的患者进入研究.采用流式细胞术检测移植物中MNC,CD34+细胞,T淋巴细胞(CD3+、CD3+CD4+及CD3+CD8+)的数量,对其中31例患者进一步检测CD4+CD25+T淋巴细胞、CD3-CD16'C+D56+NK细胞及DC的数量.按患者的每公斤体重计算出输注的移植物中以上各细胞的数量.并根据上述细胞数量的中位数分别将患者分为高数量组(>中位数)和低数量组(≤中位数),比较各高数量和低数量组aGVHD的发生情况.结果 CD3+CD4+、CD3+CD8+T淋巴细胞高数量组和相应低数量组相比,Ⅱ～Ⅳ度aGVHD的累积发生率增加,但差异无统计学意义(P值分别为0.089和0.098);CD4+CD25+T淋巴细胞高数量组Ⅲ～Ⅳ度aGVHD的累积发生率显著低于相应低数量组(P<0.05);DC1高数量组总的aGVHD累积发生率显著高于相应低数量组(P<0.05),Ⅱ～Ⅳ度aGVHD累积发生率亦明显高于相应低数量组,但差异无统计学意义(P=0.069).MNC、CD34+细胞、CD3+T淋巴细胞、CD3-CD16+CD56+NK细胞及DC2高数量组与相应低数量组比较,总的及Ⅱ～Ⅳ度aGVHD的累积发生率差异均无统计学意义(P>0.05).结论 移植物中高数量的DCl增加总的aGVHD的累积发生率;而高数量的CD4+CD25+T淋巴细胞则减少Ⅲ～Ⅳ度aGVHD的累积发生率.     

Comparison of blood and peritoneal lymphocytes from continuous ambulatory peritoneal dialysis patients, asymptomatic and with peritonitis

OBJECTIVE: The purpose of this study was to compare the characteristics of the blood immunophenotype of CAPD patients with and without peritonitis and to compare the phenotypes of peripheral blood lymphocytes (PBL) and peritoneal lymphocytes (PL) in CAPD patients with peritonitis. METHODS: Fifty-seven CAPD patients (20 with peritonitis and 37 without peritonitis) were recruited in the study (mean age 66,88 +/- 13,48, male/ female 16/21). Lymphocyte subsets (CD2+, CD3+, CD3+/4+, CD3+/8+, CD3-/16 + 56+, CD4/CD8 ratio) were quantitated by using monoclonal antibodies and dual-color flow cytometric analysis. With the above method we measured PBL in patients with and without peritonitis. In patients with peritonitis we also measured PL. RESULTS: CD2 were slightly decreased in patients with peritonitis. Those patients also had more intense CD3 + / CD4+ lymphopenia (p < 0.05) and larger expansion of NK cells (p < 0.05). Patients with peritonitis appeared to have a lower ratio of CD4/CD8 (p < 0.05). All the above results are shown to Table 2. Following the onset of peritonitis, a consistent finding in all patients was a significant increase in CD2 population of PL compared with PBL (85.71 +/- 9.20 versus 82.60 +/- 7.34, p < 0.05) as well as in CD3 population (77.01 +/- 13.09 versus 68.74 +/- 13.43, p < 0.05). An increased number of CD3/8 in PL compared with PBL (33.70 +/- 9.34 versus 27.98 +/- 10.77, p < 0.05) was also noted. CONCLUSIONS: In the present study, we found important immune activation in asymptomatic CAPD patients. The activation increases during peritonitis. The causes and the clinical consequences of chronic activation remain unknown.     

腹腔镜与开腹结直肠癌根治术对机体免疫系统影响的比较研究

目的:比较腹腔镜手术与传统开腹手术对患者免疫机能的影响。方法:2006年12月至2007年7月收治结直肠癌患者60例,分别行腹腔镜手术和开腹手术各30例,于术前1d和术后第3天、第7天抽取外周静脉血,比较两组患者的C反应蛋白,IgA,IgM,IgG,IL-6,CD3+,CD4+,CD8+细胞和NK细胞,比较术前1d和术后第1天、第3天TNF-α细胞活性。结果:术后第3天患者CD3+,CD4+,CD8+细胞活性及CD4+/CD8+差异无显著性,但术后第7天腹腔镜较开腹组明显低。术后第3天IL-6开腹组明显高于腹腔镜组。C反应蛋白于术后第3天开腹组高于腹腔镜组。IgM于术后第3天开腹组高于腹腔镜组,IgA、IgG无显著统计学意义。TNF-α于术后第3天开腹组高于腹腔镜组。结论:腹腔镜结直肠癌根治术较传统开腹手术对机体免疫机能影响较小。     

恶性重度梗阻性黄疸对机体免疫功能的影响及免疫增强剂的治疗作用

目的 探讨恶性重度梗阻性黄疸对机体免疫功能的影响及免疫增强剂的治疗作用。方法 选择我院2010年3月至2012年7月收治的无明显黄疸（TBil＜17.1μmol/L）的胆石症患者（A组,无黄疸对照组,n=20）,恶性非重度梗阻性黄疸患者（TBil17.1～342μmol/L）（B组,恶性非重度黄疸组,n=20）,恶性重度梗阻性黄疸（TBil＞342μmol/L）行经皮经肝穿刺胆管引流术（PTCD）患者（C组,恶性重度黄疸组,n=39）。其中C组又分成免疫增强剂治疗组（C1,n=18）和非治疗组（C2,n=21）。C1组PTCD术后当天开始给予注射用胸腺肽α-1,1.6 mg/d,皮下注射,连用7 d。比较各组血浆细胞因子（IL-2、IFN-α、TNF-α）、T淋巴细胞亚群（CD3+、CD4+、CD8+）和NK细胞百分率的变化。结果 C组CD3+、CD4+、CD8+、NK细胞百分率及IL-2明显低于A组（P＜0.05）,CD3+、CD8+百分率及IL-2明显低于B组（P＜0.05）;TNF-α、IFN-αC组明显高于A组和B组（P＜0.05）;B组CD3+、NK细胞百分率及IL-2明显低于A组（P＜0.05）;CD4+/CD8+比值各组间无明显差异。C1组CD3+、CD4+百分率,CD4+/CD8+比值及IL-2呈升高趋势,TNF-α、IFN-α呈降低趋势,胸腺肽α-1治疗后第5天CD3+、CD4+百分率明显高于C2组（P＜0.05）,第7天CD4+百分率、CD4+/CD8+比值、IL-2、IFN-α明显高于C2组（P＜0.05）,TNF-α明显低于C2组（P＜0.05）。结论 恶性梗阻性黄疸患者免疫功能降低,重度黄疸时免疫功能受损更加明显。免疫增强剂可明显改善恶性梗阻性黄疸患者的免疫功能。     

Type II enteropathy-associated T-cell lymphoma: a distinct aggressive lymphoma with frequent γδ T-cell receptor expression

Enteropathy-associated T-cell lymphoma (EATL), an uncommon lymphoma of intestinal intraepithelial T lymphocytes, occurs with a higher frequency in northern Europe due to association with celiac disease. Data on the occurrence of EATL in the Asian population, among whom celiac disease is very rare, are conflicting. This study aimed to characterize EATL encountered in the Chinese population in Hong Kong. Eighteen cases were identified, all fulfilling the criteria of type II rather than classical EATL. The patients, including 13 men and 5 women, had a median age of 62 years. Most presented with small bowel perforation, and there was no history of malabsorption. The clinical course was aggressive, with 14 of 16 patients dying of progressive disease or complications, usually within 1 year. The histologic features were practically identical in all cases. The central zone of the tumor showed ulceration with or without perforation and was characterized by monotonous transmural infiltration of the bowel by small-sized or medium-sized lymphoma cells with few admixed inflammatory cells and no coagulative necrosis. The peripheral zone featured lateral spread of lymphoma cells in the mucosa, accompanied by variable involvement of the submucosa and muscularis. In all cases, there was an intraepithelial lymphocytosis zone contiguous or discontinuous with the peripheral zone, which was characterized by infiltration of the intestinal epithelium by nonatypical small lymphocytes, and not accompanied by other histologic changes of enteropathy. The most common phenotype of the lymphoma cells was CD3+, CD5-, CD4-, CD8+, CD56+, TIA1+, CD30-, and Epstein-Barr virus, and 2 cases showed aberrant expression of CD20. A remarkable finding was that 14 (78%) cases expressed γδ T-cell receptor, and only 6 (33%) expressed αβ T-cell receptor (with 3 cases coexpressing both T-cell receptors and 1 case expressing neither). The immunophenotype of the intraepithelial lymphocytes was either discordant (particularly with respect to CD8 and CD56 expressions) or concordant with the lymphoma cells of the corresponding cases. Thus, this study shows that EATL occurring in the Chinese population is exclusively of type II. In contrast to several studies, intraepithelial lymphocytosis can be consistently demonstrated and this component seems to represent a precursor lesion of EATL rather than a manifestation of celiac disease. In view of the differences in epidemiology and clinicopathologic features, we believe it is justified to separate out type II EATL from the EATL category as a distinct form of lymphoma, for which we propose the designation "monomorphic intestinal T-cell lymphoma."