A high frequency of peripheral blood NKG2D+NK and NKT cells in euthyroid patients with new onset hashimoto’s thyroiditis—a pilot study

Hashimoto’s thyroiditis (HT) is a T cell-mediated autoimmune disease. However, little is known about the role of different subsets of natural killer (NK) and natural killer T (NKT) cells at the early stage of the HT process. A total of 45 euthyroid patients with new onset HT and 40 age/gender-matched healthy controls (HC) were examined for the frequency of different subsets of NK and NKT cells and their function by flow cytometry. In comparison with that in HC, significantly higher percentages of peripheral blood CD3-CD56+ NK, NKG2D+, NKp30+ NK and NKT cells, but significantly lower percentages of NKG2A+, KIR2DL3+ inhibitory NK and NKT cells were detected in the HT patients. Furthermore, the percentages of NKG2D+ NK cells were correlated positively with the concentrations of serum anti-thyroid peroxidase antibody (TPOAb) in the HT patients. Moreover, the percentages of inducible IFN-γ and CD107a+ NK cells in the HT patients were significantly higher than those in HC. Our data suggest that activated NK cells may participate in the early pathogenic process of HT.     

Differential distribution of NK cells in decidua basalis compared with decidua parietalis after uncomplicated human term pregnancy

As pregnancy progresses, a characteristic decline in the percentage of CD56bright CD16- uterine natural killer (NK) cells occurs. Studies of term decidua, however, have focused only on leukocytes derived from decidua basalis, the site of implantation. The decidua parietalis, lining the remainder of the uterine cavity is another important region of the maternal-fetal interface that forms contact with fetal tissue at the end of the first trimester. The aim of this study was to evaluate possible differences in expression of CD16 and CD56 on leukocytes from normal term decidua basalis and decidua parietalis. Decidua basalis and parietalis samples were obtained from 30 placentas collected after elective cesarean section. Percentages of leukocyte subpopulations and NK cell subsets within the CD45+ cell fraction were determined by flow cytometry. In six decidual samples, concurrent immunohistochemical staining was performed. Higher percentages of CD56dim CD16+ NK cells and CD56- CD16+ cells were found in decidua basalis in comparison to decidua parietalis. In contrast, the percentage of CD56bright CD16- uterine NK cells was significantly higher in decidua parietalis. Immunohistochemical quantification supported flow cytometric results. We conclude that significant differences exist with respect to the distribution of NK cells in term decidua basalis and parietalis. Future functional studies may improve our understanding of their role at the maternal-fetal interface.     

The expression of killer cell inhibitory receptors on natural killer cells and activation status of CD4+ and CD8+ T cells in the decidua of normal and abnormal early pregnancies.

The establishment of the human placenta in early pregnancy is characterized by the presence of large numbers of natural killer cells within the maternal decidua. These NK cells have an unusual phenotype, CD3- CD16- CD56(bright), distinguishing them from peripheral blood NK cells. They may control trophoblast migration and placentation. Using a panel of monoclonal antibodies to several members of the KIR family and flow cytometry, we found that KIRs are expressed on decidual NK cells. There is variation in both the percentage of cells expressing a particular receptor and the density of receptor expression between decidual NK cells from different individuals. In anembryonic pregnancy, the proportions of decidual NK cells with a particular KIRs (GL183 and EB6) decreased significantly when compared with normal pregnancy (p = 0.01 and 0.01, respectively), raising the possibility that these NK receptors may be involved in recognition of the allogeneic fetus by the mother at the implantation site. In the decidua, more CD4+ and CD8+ T cells expressed CD69 and HLA-DR than in blood, indicating that T cells are regionally activated during early pregnancy. When compared with normal pregnancy, decidual HLA-DR+CD4+CD3+, CD69+CD8+CD3+ and HLA-DR+CD8+CD3+ T lymphocytes are significantly increased in anembryonic pregnancy. The over-activation of decidual T cells during anembryonic pregnancy may thus contribute to the increased NK cytotoxicity activity.     

米非司酮对早孕外周血和蜕膜组织自然杀伤细胞亚群的影响

目的和方法：采用流式细胞仪检测淋巴细胞亚群法,探讨米非司酮对早孕外周血和蜕膜ＮＫ细胞亚群的影响。结果：早孕和米非司酮处理组外周血的ＮＫ细胞各亚群的百分率近似;米非酮处理组血清Ｅ２和Ｐ４均稍高于早孕组。而早孕蜕膜组的三个ＮＫ细胞亚群的百分率均明显高于米非司酮处理组。米非司酮处理组的蜕膜以ＣＤ５６Ｎ炙主要淋巴细胞亚群,而外周血则以ＣＤ５６ＣＤ１６和ＣＤ１６ＮＫ细胞为主。结论：米非司酮主要作用于早孕母胎     

Deficiency of decidual IL-10 in first trimester missed abortion: a lack of correlation with the decidual immune cell profile

PROBLEM: To determine if first trimester missed abortion decidua is characterized by an altered immune cell profile and/or a modified interleukin (IL)-10 and interferon (IFN)-gamma production pattern compared with decidua from elective termination. METHOD OF STUDY: Flow cytometry and immunohistochemistry techniques were used to determine the decidual immune cell phenotypic profile and production pattern of IL-10 and IFN-gamma in cases of elective termination (n = 14) and missed abortion (n = 12). RESULTS: Both groups had a similar proportion of CD56+ CD16-, CD56+ CD16+, CD19+, CD3+, CD4+, CD8+, alphabeta T cells and gammadelta T cells. The majority of alphabeta and gammadelta positive T cells in both groups coexpressed the natural killer (NK) cell marker CD56, but lacked cell surface expression of CD3. Diminished decidual IL-10 staining was noted in 7/10 missed abortion cases compared with none of the elective termination cases (n = 12) (P = 0.007). A uniform decidual IFN-gamma staining pattern was observed in both groups. CONCLUSION: Decreased IL-10 production coupled with a sustained IFN-gamma presence noted in missed abortion compared with elective termination cases suggest that these cytokines may be important determinants in pregnancy outcome. In contrast, differences in the proportion of immune cells between both groups may not be a critical factor in early pregnancy loss. In normal pregnancy, decidual alphabeta and gammadelta positive T cells with reduced CD3 on their cell surface may be intrinsically restricted in T-cell receptor (TCR)-mediated activation.     

CD28-negative cytolytic effector T cells frequently express NK receptors and are present at variable proportions in circulating lymphocytes from healthy donors and melanoma patients.

In humans, NK receptors are expressed by natural killer cells and some T cells, the latter of which are preferentially alphabetaTCR+ CD8+ cytolytic T lymphocytes (CTL). In this study we analyzed the expression of nine NK receptors (p58.1, p58.2, p70, p140, ILT2, NKRP1A, ZIN176, CD94 and CD94/NKG2A) in PBL from both healthy donors and melanoma patients. The percentages of NK receptor-positive T cells (NKT cells) varied strongly, and this variation was more important between individual patients than between individual healthy donors. In all the individuals, the NKT cells were preferentially CD28-, and a significant correlation was found between the percentage of CD28- T cells and the percentage of NK receptor+ T cells. Based on these data and the known activated phenotype of CD28- T cells, we propose that the CD28- CD8+ T cell pool represents or contains the currently active CTL population, and that the frequent expression of NK receptors reflects regulatory mechanisms modulating the extent of CTL effector function. Preliminary results indicate that some tumor antigen-specific T cells may indeed be CD28- and express NK receptors in vivo.     

HIV原发感染者自然杀伤样T细胞NKG2A/NKG2D变化的研究

目的深入了解人类免疫缺陷病毒(human immunodeficiency virus,HIV)原发感染者(primary HIV infection,PHI)NKT样细胞表面NKG2A/NKG2D受体表达的变化。方法选取25例未经高效抗逆转录病毒治疗的HIV原发感染者和27例HIV抗体阴性健康对照,用流式细胞仪检测研究对象外周血NKT样细胞表面NKG2D和NKG2A的表达。结果 HIV原发感染者NKT样细胞绝对数和百分率显著低于健康对照(P<0.01)。HIV原发感染者NKT样细胞表面NKG2A、NKG2D受体表达与健康对照并无显著差异。HIV原发感染者病毒调定点低组NKG2A+NKT样细胞、NKG2A+NKG2D-NKT样细胞以及NKG2A+NKG2D+NKT样细胞百分率均显著低于病毒调定点高组(P<0.05);NKT细胞绝对数和百分率、NKG2D+NKT样细胞、NKG2D+NKG2A-NKT样细胞百分率在两组间相似,没有显著性差异。NKG2A+NKT细胞的百分比与病毒载量正相关(R=0.430,P=0.032)。结论 NKT样细胞数量以及其表面NKG2A受体的表达可作为HIV疾病进程的预测指标之一。     

No difference in natural killer or natural killer T-cell population, but aberrant T-helper cell population in the endometrium of women with repeated miscarriage

BACKGROUND: The aim of this study was to assess the natural killer (NK) cell and natural killer T (NKT) cell populations and cytokine expression of T-helper (Th) cells in the endometrium of women who suffered from unexplained repeated miscarriage (RM). METHODS: The percentages of NK cells, NKT cells and CD4(+) cells expressing intracellular interferon (IFN)-gamma, interleukin (IL)-4 and tumour necrosis factor (TNF)-alpha were measured by flow cytometry in the endometrium of 20 RM women and 17 fertile control women in the mid-luteal phase of the menstrual cycle. RESULTS: No significant differences in CD56(+) NK cell or CD3(+)CD4(-)CD8(-)Valpha24(+)Vbeta11(+) NKT cell percentages were found between RM and control women. However, in RM women compared with control women, the percentages of CD3(+) cells (mean 40.3 versus 56.5%), CD4(+)IFN-gamma(+) cells (28.4 versus 39.5%) and CD4(+)TNF-alpha(+) cells (32.9 versus 45.8%) were significantly lower. The Th1/Th2 cell balance in RM women did not differ from that of controls. CONCLUSIONS: Immunodystrophism detected as diminution of the Th cell population rather than Th1 predominance, NK cell or NKT cell accentuation in the endometrium might underlie the pathophysiology of unexplained RM. This finding provokes an additional controversy on the Th1/Th2 balance concerning RM aetiology.     

NKT细胞、NK细胞和T细胞亚群在活动性肺结核患者外周血的表达及意义

目的:探讨活动性肺结核病人外周血CD3+T、CD3+CD4+Th、CD3+CD8+Tc、CD3-CD16+56+NK、CD3+CD16+56+NKT、Th/Tc的表达变化及其临床意义。方法:采用流式细胞术分析45例肺结核病人、16例肺部感染病人及30例健康人外周血CD3+Th、CD3+CD4+Th、CD3+CD8+Tc、CD3-CD16+56+NK、CD3+CD16+56+NKT、Th/Tc的表达和变化情况。结果:初、复治肺结核患者的外周血NKT比例明显高于健康人(P<0.05);Th低于健康人(P<0.05);Tc高于健康人(P<0.05);Th/Tc低于健康人(P<0.05)。初、复治肺结核患者之间T、Th、Tc、NK、NKT、Th/Tc未见明显差异。肺部感染、活动进展Ⅰ期、活动进展Ⅱ期病人NKT阳性细胞数高于健康人和吸收好转期病人且结果有统计学意义(P<0.05);活动进展Ⅱ期组高于肺部感染组且结果有统计学意义(P<0.05)。活动进展Ⅰ期、活动进展Ⅱ期病人Tc阳性细胞数高于健康人组且结果有统计学意义(P<0.05)。Th/Tc吸收好转期、肺部感染、活动进展期、活动进展Ⅱ期均低于健康人组且结果有统计学意义(P<0.05)。轻症、中症、重症患者,重症者Th升高、Tc下降、Th/Tc升高。结论:NKT细胞与肺结核的发展和转归有关。Tc细胞的升高是免疫系统对于结核杆菌的反应,与肺结核病变的发展、范围和程度紧密相关。重点监测外周血NKT细胞和Tc细胞对于掌握活动性肺结核发展和预后有特殊的意义。     

Elevated gamma interferon-producing NK cells, CD45RO memory-like T cells, and CD4 T cells are associated with protection against malaria infection in pregnancy

Previous studies have shown that gamma interferon (IFN-gamma) production in the placenta is associated with protection against placental malaria. However, it remains unknown which IFN-gamma-producing cell subpopulations are involved in this protection and whether the cellular immune components of protection are the same in the peripheral and the placental blood compartments. We investigated cell subpopulations for CD4, CD8, and CD45RO memory-like T cells and CD56+/CD3- natural killer (NK) cells and for IFN-gamma production by these cells in maternal peripheral and placental intervillous blood in relation to the status of malaria infection in pregnancy. Of 52 human immunodeficiency virus-negative enrolled pregnant women residing in Western Kenya, 20 had placental parasitemia. We found that the percentages of CD45RO memory-like and CD4 T cells were significantly higher in the periphery than in the placenta, while the CD56/CD3- NK-cell percentage was higher in the placenta than in the periphery, suggesting differences in immune cell profiles between the two blood compartments. Furthermore, the percentages of peripheral CD45RO memory-like and CD4 T cells were significantly elevated in aparasitemic women compared to levels in the parasitemic group, with aparasitemic multigravid women having the highest percentages of CD45RO memory-like and CD4 T cells. In contrast, at the placental level, IFN-gamma production by innate NK cells was significantly increased in aparasitemic women compared to parasitemic women, regardless of gravidity. These results suggest that the elevated IFN-gamma-producing NK cells in the placenta and CD45RO memory-like and CD4 T cells in peripheral blood may be involved in protection against malaria infection in pregnancy.     

Role of decidual natural killer (NK) cells in patients with missed abortion: differences between cases with normal and abnormal chromosome.

In order to study the mechanism of abortion, the proportions of NK cells in the peripheral blood and decidual lymphocytes were evaluated in both chromosomally normal and abnormal missed abortions. In normal pregnancy, CD56+16-3- NK cells are a major element of decidual lymphocytes. The percentages of CD56+16-3-NK cells of peripheral lymphocytes in normal pregnancies were not statistically significantly different from those of chromosomally normal and abnormal abortions. In the decidua, the percentages of CD56+16-3- NK cells of decidual lymphocytes showed no statistically significant differences between normal pregnancies and chromosomally abnormal abortions. However, the percentages of CD56+16-3-NK cells of chromosomally normal abortions were lower than those of chromosomally abnormal (P = 0.0025). Moreover, the percentages of CD56+16- NK cells in abortions with normal chromosomes were lower than those in normal pregnancies or abortions with abnormal chromosomes (P = 0.0037, P = 0.0025). However, when the proportion of CD56+ NK cells expressing CD16 was evaluated, there were no statistically significant differences in the percentages of CD56+16+ NK cells in normal pregnancies and missed abortions with normal chromosomes and abnormal chromosomes. We conclude that the expression of decidual CD56+16-3- NK cells in missed abortions with normal chromosomes is different from abortions with abnormal chromosomes and that this phenomenon may depend on an abnormal immune response of the maternal side.     

Profiles of NK, NKT cell activation and cytokine production following vaccination against hepatitis B

Human natural killer (NK) cells (CD56+ CD3-) represent crucial components of the innate immune system especially against viral infections and because their activation can modulate the outcome of the adaptive immune response. NKT cells (CD56+CD3+), a lymphocyte T population characterized by expression of surface markers of NK cells, are known to be abundant in the liver and their activation could be associated with hepatic injury. Using three-color flow cytometry to measure surface receptors and intracellular cytokines, we have explored early activation signals and cytokine production in NK and NKT cells within a group of hepatitis B vaccinated and non-vaccinated individuals. A specific increase of the CD56bright cell population, the activation receptor CD69 and IFN-gamma, was observed in NK cells following incubation with recombinant HBsAg in responders to vaccination. Comparable results were observed in NKT cells showing an increment of CD69, CD25, IL-2 and IFN-gamma expression in responder subjects. These parameters were statistically diminished in non-responder individuals (p<0.05) in both groups of cells. These results demonstrate a diminished activation of these cells in non-responders to the vaccine, suggesting that NK and NKT cells play an important role in the immune response following hepatitis B vaccination.     

Decidual natural killer cells in recurrent spontaneous abortion with normal chromosomal content.

PROBLEM: The maternal local immune responses in unexplained recurrent spontaneous abortion (RSA) are not yet well known. Maternal peripheral and decidual natural killer (NK) cells were evaluated in RSA with normal chromosomal content. METHOD OF STUDY: Maternal peripheral blood, villous trophoblast, and decidua were taken from 15 normal pregnancies and 9 RSA patients with normal chromosomes. The NK cells in decidual lymphocytes were evaluated by flow cytometry using monoclonal antibodies for CD56, CD16, and CD3. RESULTS: The percentages of CD56+ CD16- CD3- cells in decidual lymphocytes in RSA were lower than in normal pregnancies (P < 0.002). The CD56+CD16+/CD56+CD16- cells ratio in RSA was higher than in normal pregnancies (P < 0.02). CONCLUSION: The lower percentages of CD56+CD16-CD3- cells in RSA cases may show an inappropriate accumulation of NK cells in the decidua, and this finding may be a factor involved in RSA.     

Proportion of CD56+3+ T cells in decidual and peripheral lymphocytes of normal pregnancy and spontaneous abortion with and without history of recurrent abortion

PROBLEM: The present study investigated the proportion of CD56+3+ T cells in maternal peripheral and decidual lymphocytes in normal pregnancy and spontaneous abortion with and without history of recurrent spontaneous abortion (RSA). METHOD OF STUDY: Maternal peripheral blood and decidua were taken from normal pregnancies and missed abortions with and without RSA. Decidual lymphocytes were prepared from decidual tissue and analyzed by flow cytometry. RESULTS: In normal pregnancy, the percentages of CD56+3+ T cells in decidual lymphocytes did not differ from those in the peripheral blood. However, the proportion of CD56+3+ T cells in decidual CD3+ T cells increased higher than that in the peripheral CD3+ T cells. The percentages of decidual CD56+3+ T cells in missed abortions with and without RSA were lower than those in normal pregnancies. CONCLUSION: CD56+3+ T cells may play a role in the maintenance of pregnancy. The phenomenon, where the proportion of CD56+3+ T cells in decidual lymphocytes decreases, may be due to an immunologic event leading to missed abortion.     

不明原因自然流产与蜕膜NK细胞表面活化性受体表达的相关性研究

探讨不明原因自然流产患者蜕膜NK细胞杀伤活性与其细胞表面活化性受体NKp46、NKp44、NKp30和NKG2D表达的相关性。选取21例早孕不明原因自然流产患者为病例组,25例正常早孕人流妇女为对照组,收集两组的蜕膜组织,Ficoll密度梯度离心分离淋巴细胞,MACS磁珠分选CD3-CD56+NK细胞。以K562细胞为靶细胞,用细胞染色及流式细胞技术检测两组蜕膜NK细胞杀伤活性,用流式细胞技术检测两组蜕膜CD56brightCD16-NK和CD56dimCD16+NK细胞上活化性受体NKp46、NKp44、NKp30和NKG2D的表达,并与NK细胞杀伤活性进行相关性分析。结果:(1)早孕蜕膜NK细胞具有杀伤活性;(2)病例组蜕膜NK细胞的杀伤活性较正常对照组显著增强(P=0.014);(3)病例组蜕膜CD56brightCD16-NK细胞中NKp44的表达比正常对照组显著升高(P=0.021);病例组蜕膜CD56dimCD16+NK细胞中NKp46和NKp44的表达比正常对照组显著升高(分别P=0.026,P=0.041);其余活化性受体的表达两组未见明显差异;(4)蜕膜NK细胞杀伤功能与蜕膜CD56brightCD16-NK细胞中NKp44的表达呈显著正相关(r=0.677,P<0.05),和蜕膜CD56dimCD16+NK细胞中NKp46的表达呈显著正相关(r=0.634,P<0.05)。蜕膜NK细胞活化性受体NKp46和NKp44表达增加,从而使蜕膜NK细胞的杀伤功能增强可能在不明原因自然流产的发病中起重要作用。     

Expression of killer inhibitory receptors on cytotoxic cells from HIV-1-infected individuals

Dysfunction of cytotoxic activity of T and natural killer (NK) lymphocytes is a main immunological feature in patients with AIDS, but its basis are not well understood. It has been recently described that T and NK cell-mediated cytotoxicity can be regulated by HLA killer inhibitory receptors (KIR). In this work, we have determined on cytotoxic T cells and NK cells from HIV-1-infected individuals the expression of the following KIR molecules: p58, p70, and ILT2 (immunoglobulin-like family KIR) as well as CD94 and NKG2A (C-lectin-type family KIR). With some exceptions, no significant changes were found on the expression of immunoglobulin-like KIR in either CD8+ or CD56+ cells. Interestingly, the percentages of CD8+ and CD56+ cells expressing CD94 were significantly increased in these individuals. We also show that, in vitro, IL-10 up-regulates CD94 expression on CD8+ and CD56+ cells obtained from normal individuals, suggesting that the augmented expression observed in HIV-infected individuals could be related to the high levels of IL-10 previously described in HIV-1-infected individuals.     

补肾中药对溴隐亭致流产鼠模型中蜕膜CD56~+NK细胞表面CD69和CD94表达的影响

为了观察补肾中药是否能影响蜕膜CD5 6 + NK细胞比例及其表面CD6 9、CD94的表达 ,从而进一步阐明补肾中药对母胎界面免疫的影响机制。SD大鼠于孕 6～ 8d皮下注射溴隐亭 0 3mg/kg·d ,建立改良的溴隐亭致SD大鼠流产模型 ,随机分为三组。A组为模型组 ;B、C组在孕 1～ 1 1d分别给予大剂量中药 (4 5g/kg·d)、P(8mg/kg·d) ,另设正常孕鼠对照 (D组 )。孕 1 2d处死 ,取蜕膜组织 ,分离成单个细胞悬液 ,用流式细胞分析技术观察 4组蜕膜CD5 6 + NK细胞的量及蜕膜NK细胞表面CD6 9、CD94的表达差异。结果发现 :B组 (P <0 0 5 )、C、D组 (P <0 0 1 )妊娠率与A组相比增加 ,并且有差异 ;B、C组蜕膜CD5 6 + NK细胞比例与A组相比明显增加 ,与D组无差异 ;各组蜕膜CD5 6 + NK细胞表面CD6 9表达无差异 ;B、C、D组CD94的表达与A组相比显著增加 ;A组蜕膜CD5 6 + NK细胞表达CD6 9与CD94相比明显增加 ,B、C组相反。因此 ,补肾中药能影响蜕膜CD5 6 + NK细胞表面CD6 9、CD94的表达 ,可能通过增加CD94的表达 ,抑制CD6 9从而进一步抑制NK细胞的活性 ,起到保胎作用     

早孕妇女外周血和蜕膜组织中自然杀伤细胞亚群的变化

目的和方法：用流式细胞仪检测正常非孕及早孕妇女外周血和蜕膜自然杀伤细胞表面标记ＣＤ５６和ＣＤ１６分子,探讨早孕外周血与蜕之间自然杀伤细胞亚群的差异以及雌、孕激素对外周血自然杀伤细胞的影响。结果：蜕膜以ＣＤ５６细胞为主要淋巴细胞,早孕外周血则以ＣＤ５６ＣＤ１６和ＣＤ１６为主。孕酮在一定范围内增加,可使外周血自然杀伤细胞各亚群的百分率明显增加;在早孕期、雌、孕激素水平的急剧升高可能使外周血ＣＤ５６细胞     

Decidual T lymphocyte activation in hydatidiform mole

AIM: To quantify and compare decidual leucocyte subpopulations in complete and partial hydatidiform molar pregnancy with those in normal early pregnancy. METHODS: Decidual leucocytes were characterised using an avidin-biotin technique and a panel of monoclonal antibodies in formalin fixed, paraffin embedded decidual tissues from 10 normal first trimester pregnancy terminations and from 13 partial and 13 complete hydatidiform moles. Immunostained cells were fully quantitated and differences between subject groups were analysed using the Mann-Whitney test. T lymphocyte populations were further characterised using double immunohistochemical labelling. RESULTS: The numbers and percentages of CD3+ and CD4+ T cells were significantly increased in complete hydatidiform moles compared with partial moles and normal early pregnancy decidua. No differences were found in the number or percentage of CD8+ T cells. The CD8+ to CD4+ T cell ratio decreased significantly in complete mole compared with partial mole and normal decidua. The numbers and percentages of CD45RO+ cells increased significantly in both partial and complete hydatidiform mole compared with normal first trimester decidua. Double labelling confirmed that 50% of CD3+ T cells in complete and partial molar pregnancy coexpressed CD45RO, compared with 30% in normal pregnancy. Other leucocyte populations (eGLs, macrophages, B cells, and classical natural killer cells) did not differ between complete and partial mole and normal pregnancy decidua. CONCLUSIONS: The presence of an increased population of activated decidual CD45RO+ T cells in complete and partial molar pregnancy suggests altered maternal immune responses against molar trophoblast.     

Changes in natural killer cell phenotype in patients with post-viral fatigue syndrome.

We analysed peripheral blood CD56+ natural killer (NK) cell subsets in 23 carefully characterized patients with post-viral fatigue syndrome (PFS), compared with 19 healthy controls, using fluorochrome-conjugated, specific monoclonal antibodies and the FACScan. We found significantly increased percentages of CD56+, and especially CD56bright+ NK cells in PFS patients. We also found significantly increased percentages of CD56+ high affinity interleukin-2 (IL-2) receptor (CD25)+ and CD56+ transferrin receptor (CD71+) subsets of cells, most of which also stained brightly for CD56. Also, we found an increased percentage of CD56+ CD3+ cells, many of which stained brightly for CD56, although there was no increase in the percentage of CD56- CD3+ T cells in these patients. These observations, in conjunction with very low percentage of CD56- CD25+ cells, suggest that there is a preferential involvement of this minor subset of CD56+ CD3+ T cells in PFS. Finally, a decreased percentage of CD56+ Fc gamma receptor (CD16)+ NK cells was identified, which suggests a reduced capacity of antibody-dependent cellular cytotoxicity in PFS patients. Subsets of CD56+ NK cells co-expressing CD2, CD4 or CD8 did not show any significant difference between PFS patients and healthy controls. These phenotypic changes provide laboratory evidence of immunological abnormalities in this syndrome, and, we suggest, may be consistent with persistent viral infection.