T lymphocyte subsets in patients with malignant melanoma

Summary T lymphocyte subset profiles were determined by monoclonal antibodies on cryopreserved peripheral blood lymphocytes from 57 patients with malignant melanoma and 19 healthy controls. Quantitation of percentages of total T cells (OKT3.PAN), helper (OKT4.IND) or suppressor (OKT8.SUP) cells, and the ratio of helper/suppressor subsets revealed no correlation of these markers with stage of disease or clinical outcome. A sequential study of these markers on peripheral blood lymphocytes from three stage I melanoma patients with subsequent recurrent disease showed no fluctuations that could be correlated to tumor progression. This study indicates that there is no systemic imbalance in T cell subsets in malignant melanoma and that quantitation of these subsets cannot predict the clinical course of this disease.     

传染性单核细胞增多症患者外周血T细胞亚群检测及临床意义

目的 检测传染性单核细胞增多症(IM)患者及非本病的发热患者外周血T淋巴细胞亚群,探讨EB病毒感染导致的传染性单核细胞增多症的免疫反应机制及与非本病发热患者的鉴别诊断价值,同时通过检测患者血液中的EBV-DNA载量加以确证.方法 选取确诊为传染性单核细胞增多症的患者30例(IM组),非传染性单核细胞增多症的发热患者30...     

Differential loss of T cell signaling molecules in metastatic melanoma patients' T lymphocyte subsets expressing distinct TCR variable regions

In this study we tested the hypothesis that loss of T cell signaling molecules in metastatic melanoma patients' T cells may affect differently T cell subsets characterized by distinct TCR variable regions. By a two-color immunofluorescence technique, expression of zeta-chain, lck, and ZAP-70 was evaluated in CD3+ T cells and in three representative T cell subsets expressing TCRAV2, TCRBV2, or TCRBV18. Partial loss of lck and ZAP-70 was found in CD3+ T cells from PBL of most melanoma patients, but not of healthy donors. The extent of zeta-chain, lck, and ZAP-70 loss depended on the TCRV region expressed by the T cells, and this association was maintained or increased during progression of disease. Coculture of patients' or donors' T cell with melanoma cells, or with their supernatants, but not with normal fibroblasts or their supernatants, down-modulated expression of zeta-chain, lck, and ZAP-70 in a TCRV region-dependent way. Immunodepletion of soluble HLA class I molecules present in tumor supernatants, but not of soluble ICAM-1, blocked the suppressive effect on T cell signaling molecule expression. T cell activation with mAbs to a single TCRV region and to CD28 led to significant and TCRV region-specific re-induction of zeta-chain expression. These findings indicate that extent of TCR signaling molecules loss in T lymphocytes from metastatic melanoma patients depends on the TCRV region and suggest that tumor-derived HLA class I molecules may contribute to induce such alterations.     

肠道微生物与2型糖尿病患者T淋巴细胞亚群和炎症因子水平的相关性

探究肠道微生物与2型糖尿病（T2DM）患者T淋巴细胞亚群和炎症因子水平的相关性。

选择2019年4月到2022年4月我院收治的94例T2DM患者作为T2DM组,另选体检健康者81例作为对照组,采集所有受试者外周血及粪便样本,检测空腹血糖（FPG）、胰岛素抵抗指数（HOMA-IR）、空腹胰岛素（FINS）、炎症因子IL-6、hs-CRP水平、T淋巴细胞亚群（CD3⁺、CD4⁺、CD8⁺）水平和主要肠道菌群丰度,分析主要肠道菌群变化与CD4⁺/CD8⁺、IL-6、hs-CRP的关系。

治疗后T2DM组FBG、FINS、HOMA-IR、IL-6、hs-CRP水平均高于对照组（P＜0.05）,T2DM组CD3⁺、CD4⁺、CD8⁺及CD4⁺/CD8⁺比值均低于对照组（P＜0.05）。T2DM组肠道双歧杆菌、乳酸杆菌数量、B/E值低于对照组,大肠杆菌、肠球菌数量高于对照组（P＜0.05）。Pearson相关性分析显示：T2DM患者双歧杆菌、乳酸杆菌、B/E值与IL-6、hs-CRP水平呈负相关,与CD4⁺/CD8⁺比值呈正相关（P＜0.05）;大肠杆菌、肠球菌数量与IL-6、hs-CRP水平呈正相关,与CD4⁺/CD8⁺比值呈负相关（P＜0.05）。

T2DM患者肠道菌群失调、定植力受损,这可能与其能引发患者CD4⁺/CD8⁺水平降低和炎症因子IL-6、hs-CRP水平升高有关。

     

A preliminary study of human pineal gland concretions: structural and chemical analysis

Acervuli and fragments of pineal gland obtained from 33 subjects of both sexes and age ranging from 1 to 87 years, (30 autopsy and 3 biopsy specimens) were analyzed by light microscopy, transmission and scanning electron microscopy, X-ray diffraction and X-ray energy dispersive microanalysis. It was found that primary mineralization occurs in an organic matrix formed by pinealocytes and that hydroxyapatite also takes place in mineral deposition. From our analysis, the formation of acervuli appears to be age and sex independent and can be possibly related to the secretory activity of the gland.     

肠道菌群对肠黏膜T淋巴细胞亚群的调节作用

肠道菌群在肠道免疫稳态中起到了至关重要的作用。大量研究表明肠道菌群通过调节T淋巴细胞亚群的增殖、分化和T细胞亚群分泌不同的细胞因子,可以改变肠道免疫系统的状态。本研究综述了肠道微生物对主要T淋巴细胞亚群的调节作用。     

小细胞肺癌患者外周血淋巴细胞亚群分析

目的 探究化疗对小细胞肺癌(small cell lung cancer,SCLC)患者免疫功能的影响。 方法 选择2013年1月到2018年12月我院收治的95例小细胞肺癌患者为研究对象。患者第一周期、第二周期化疗前采用流式细胞术检测患者外周血淋巴细胞亚群水平,分别按照不同疗效及不同化疗方案对患者外周血淋巴细胞亚群进行比较。 结果 (1)化疗后,95例患者CD3+、CD4+、CD8+细胞平均值增加,CD19+、γδT细胞平均值减少,差异均有统计学意义(均P+、CD8+细胞平均值增加,CD19+细胞减少,差异有统计学意义(均P0.05)。(3)依托泊苷联合顺铂(EP)方案组化疗后患者CD3+、CD8+细胞平均值增多,CD19+细胞减少,差异均有统计学意义(均P0.05)。 结论 化疗可以调节小细胞肺癌患者的免疫功能,增强细胞免疫,降低体液免疫,其中EC方案对患者细胞免疫的增强作用较为显著。     

Alterations in γ-aminobutyric acid content in the rat superior cervical ganglion and pineal gland

The endogenous γ-aminobutyric acid (GABA) content of the rat pineal gland and superior cervical ganglion (SCG) was measured by high pressure liquid chromatography. It was found that GABA levels in both tissues increased after decapitation of the animals. The GABA content of tissues frozen within 20 seconds after decapitation was the same as that of tissues removed from animals killed by microwave irradiation. Amino-oxyacetic acid, a GABA-transaminase inhibitor, increased the endogenous GABA content of both of these tissues. Dimethylphenylpiperizinium or isoniazid administration did not alter GABA levels in these tissues. Isoproterenol increased the GABA content of the SCG but did not change the pineal gland GABA levels. The ability of the pineal gland to take up and accumulate ³H-GABA was significantly reduced in rats that had been ganglionectomized. A fluctuation in endogenous GABA levels in the pineal gland was seen to occur when measures were taken at different times of the day. These results tend to suggest that GABA may have some functional role in the pineal gland and the superior cervical ganglion.     

Functional analysis of T lymphocyte subsets in antiviral host defense

The role of different T cell subsets in antiviral host defense was investigated by treating thymectomized C57BL/6 and CBA/J mice with monoclonal rat anti-Lyt-2 or anti-L3/T4 IgG 2b antibodies 14 and 10 days before infection. This treatment depleted the respective T cell subsets to undetectable levels in peripheral blood when assayed by immunofluorescence. In mice treated with anti-Lyt-2, induction of cytotoxic T cells was reduced to less than 1 to 2% after intravenous infection with Armstrong strain of lymphocytic choriomeningitis virus (LCMV). In addition, no primary swelling of the footpad could be detected following local inoculation of the virus. In animals treated with anti-L3/T4, antiviral cytotoxic T lymphocyte responses were reduced by a factor of 10. These L3/T4+ cell-depleted mice showed delayed footpad swelling after local injection of LCMV Armstrong. After intracerebral infection with LCMV, anti-Lyt-2-treated mice were resistant and those injected with anti-L3/T4 were totally susceptible to LCMV Armstrong-triggered immunopathologic disease. Virus could be detected in the blood of antibody-treated mice 7 days after inoculation; however, no virus could be measured in the blood of surviving anti-Lyt-2-treated animals 15 days after intracerebral infection. Serum titers of interferon-alpha,beta induced by viral infection remained unaffected by depletion of T cell subsets. Anti-L3/T4 antibody-treated C57BL/6 mice failed to generate IgG antibodies against the New Jersey strain of vesicular stomatitis virus, whereas Lyt-2+ cell-depleted mice had normal antivesicular stomatitis virus (New Jersey strain) IgG antibody titers.     

变应性鼻炎患者肠道微生态变化及其与T淋巴细胞亚群的关系

探讨变应性鼻炎患者肠道微生态变化及其与T淋巴细胞亚群的关系。

回顾性分析2019年4月至2020年4月医院收治的64例变应性鼻炎患者的资料, 记为A组; 另回顾性分析同期在该院体检的58例健康者的资料, 记为B组。对比A组和B组研究对象肠道菌群多样性和丰富度的变化, 对比A组和B组研究对象血清T淋巴细胞亚群水平, 分析变应性鼻炎患者肠道菌群相对丰度与血清T淋巴细胞亚群水平的相关性。

A组研究对象肠道菌群Chao1指数和Shannon指数均低于B组(P < 0.05), A组肠道菌群门水平拟杆菌门、变形菌门、厚壁菌门的相对丰度均高于B组(P < 0.05), 放线菌门的相对丰度低于B组(P < 0.05), 属水平毛螺菌属、链球菌属的相对丰度均高于B组(P < 0.05), 肠球菌属、双歧杆菌属、棒状杆菌属的相对丰度均低于B组(P < 0.05)。主成分分析显示2组菌群样品均能明显分开, 横纵坐标的贡献率分别为48.9%和16.7%, 两坐标轴总共解释了不同细菌群落差异的65.6%, 2组群落结构差异明显(P < 0.05)。A组CD3⁺比例、CD4⁺比例和CD4⁺/CD8⁺比值高于B组(P < 0.05), CD8⁺比例低于B组(P < 0.05);采用Pearson相关性检验, 变应性鼻炎患者肠道菌群门水平拟杆菌门、变形菌门和厚壁菌门的相对丰度分别与CD3⁺、CD4⁺比例和CD4⁺/CD8⁺比值呈正相关(P < 0.05), 分别与CD8⁺比例呈负相关(P < 0.05), 放线菌门的相对丰度分别与CD3⁺、CD4⁺比例和CD4⁺/CD8⁺比值呈负相关(P < 0.05), 与CD8⁺比例呈正相关(P < 0.05);属水平毛螺菌属和链球菌属的相对丰度分别与CD3⁺、CD4⁺比例和CD4⁺/CD8⁺比值呈正相关(P < 0.05), 分别与CD8⁺比例呈负相关(P < 0.05), 肠球菌属、双歧杆菌属和棒状杆菌属的相对丰度分别与CD3⁺、CD4⁺比例和CD4⁺/CD8⁺比值呈负相关(P < 0.05), 分别与CD8⁺比例呈正相关(P < 0.05)。

变应性鼻炎患者肠道菌群多样性降低, 门、属水平菌群比例均发生改变, 菌群结构差异明显, 血清CD3⁺、CD4⁺水平和CD4⁺/CD8⁺比值升高, CD8⁺水平降低, 变应性鼻炎患者肠道菌群相对丰度与血清T淋巴细胞亚群水平相关。

     

Langerhans cells and T lymphocyte subsets in the murine vagina and cervix

Immunization in the vagina can lead to the production of specific antibodies in the luminal fluid of this organ. To help understand the immune mechanisms involved in this process, we have studied the occurrence of Langerhans cells (LCs), macrophages, natural killer cells, and T and B lymphocytes in the murine vagina and cervix during the estrous cycle. LCs in the epithelia expressed Ia, F4/80, NLDC-145, and CD45, but not Mac-1, Moma-1, and Moma-2; double-labeling demonstrated phenotypic heterogeneity in this population Ia+, NLDC-145+; Ia+, NLDC-145-; Ia+, F4/80+; Ia+, F4/80-; Ia- F4/80+. T lymphocytes of both helper and cytotoxic/suppressor types were also present in the epithelia, sometimes in close association with LCs, but natural killer cells were not observed. The stroma of the vagina and cervix contained LCs (or interdigitating cells) and macrophages but few T lymphocytes and no B lymphocytes, natural killer cells, or lymphoid nodules. These observations confirm and extend previous reports that the murine vagina and cervix contain epithelial LCs and T lymphocytes and support the suggestion that antigens in the vagina and cervix, as in the epidermis, may be recognized and presented to the immune system by epithelial LCs. However, the paucity of T cells and the absence of B cells and lymphoid nodules from the stroma suggest that antigen presentation may not occur locally but at another site such as in the draining lymph nodes.     

Imbalance of peripheral follicular helper T lymphocyte subsets in active vitiligo

Vitiligo is an autoimmune disease characterized by the presence of several autoantibodies, some of which are directed against melanocyte components and have been shown to be associated with the progression of the disease. However, the mechanism involved in the production of autoantibodies remains unclear. Follicular helper CD4⁺ T cells (TFH) are specialized in B‐cell activation and antibody production, especially the TFH cell subsets type 2 and type 17. To date, TFH cell subsets have not been studied in human vitiligo. This study in 44 vitiligo patients and 19 healthy controls showed an increase in circulating TFH cells associated with disease clinical progression. A more precise analysis of TFH cell phenotype demonstrated that vitiligo is characterized by populations of peripheral TFH cells responsible for helping B‐cell function, such as TFH type 2 and type 17 which produce Th2‐ and TH17‐related cytokines, respectively. These findings suggest a new mechanism involving TFH cell subsets in the pathogenesis of human vitiligo and leading to the production of autoantibodies and disease.     

Role of different lymphocyte subsets in human anti-viral T cell cultures

We have systematically studied uncloned human cell lines derived from anti-influenza A virus or anti-Epstein-Barr virus (EBV) bulk cultures, or from cultures highly enriched for CD4+ or CD8+ lymphocytes. The most noteworthy results are the following: (1) Anti-viral bulk cultures consisted of more than 90% of CD8+ cells in all cases. In contrast, anti-HLA cell lines are composed of approximately 50% CD8+ and 50% CD4+ cells. All of the CD8+ and CD4+ cells present in the culture were also 4B4+/2H4-. (2) In anti-viral bulk cultures, the cytolytic activity was restricted by HLA class I molecules and almost exclusively through a single HLA class I molecule. (3) Positively or negatively selected CD8+ lines showed the same restriction pattern. They grew less efficiently than bulk cultures but could be maintained in the absence of CD4+ cells. The CD4+ cells were however necessary at the beginning of the culture for the development of cytolytic anti-influenza virus CD8+ cells, whereas they were not required for the development of cytolytic anti-EBV CD8+ cells. (4) The CD4+ cell lines grew more actively than bulk cultures. A cytolytic activity for virus-infected cells was constantly detected in these culture from the third passage onward and it was always restricted by HLA class II molecules. This activity was maintained throughout the culture period. However, class II-restricted cytolytic cells were not detected during primary or secondary responses in vitro.     

T lymphocyte therapy of cancer

The rationale for the use of T lymphocytes to fight cancer is the immunogenicity of tumor cells. T cells are capable to recognize and finally to kill tumor cells. Adoptive cell transfer therapies provide the opportunity to overcome tolerogenic mechanisms by enabling the selection and activation of highly reactive T cell subpopulations and by manipulation of the host environment into which the T cells are introduced. The aim of this article is to review the possibilities, limitations and recent clinical experience with this novel anticancer treatment, namely with adoptive immunotherapy using antigen-specific T cells.     

外周血T淋巴细胞亚群及早期炎症标志物表达对老年非小细胞肺癌化疗预后的影响分析

目的评估外周血T淋巴细胞亚群及早期炎症标志物表达对老年非小细胞肺癌(NSCLC)化疗预后的影响。方法入选2015年1月至2018年12月在武汉科技大学附属孝感医院接受化疗的NSCLC患者86例为NSCLC组,另选本院常规体检的健康人群82名作为对照组,分析两组人群外周血T淋巴细胞亚群与炎症细胞的分布差异。采用Kaplan-Meier单因素生存分析不同临床参数及化疗后不同T细胞亚群和炎症细胞水平患者的生存期,采用Cox比例回归风险模型分析影响NSCLC患者预后的独立影响因素。结果与对照组比较,NSCLC组患者CD3^+(71.31±6.02比68.22±7.09)、CD4^+(40.20±5.79比36.61±7.11)、CD4^+/CD8+(1.49±0.37比1.30±0.56),CD8+(28.43±6.37比31.79±9.88)均降低,而PLT(229.73±58.84比211.32±54.18)、淋巴细胞计数(LY)(1.67±0.61比30.01±8.45)及淋巴细胞百分比(LY﹪)(25.65﹪±6.87﹪比30.01﹪±8.45﹪)均升高,差异具有统计学意义(P均<0.05)。Kaplan-Meier单因素生存分析结果显示,是否淋巴转移、远处转移及不同TNM分期的患者生存期相比,差异具有统计学意义(P均<0.05);CD8+T细胞≥31.8﹪、CD4/CD8<1.28、中性粒细胞与淋巴细胞比值(NLR)<3.16及血小板与淋巴细胞比值(PLR)<197的患者生存期较长,差异具有统计学意义(P均<0.05);Cox多因素生存分析结果显示,伴远处转移(HR=9.310)、TNM分期ⅢB-Ⅳ期(HR=1.059)、CD8+T细胞<31.8﹪(HR=2.697)、NLR≥3.16(HR=1.887)及PLR≥197(HR=2.869)是影响老年NSCLC患者预后的独立影响因素(P均<0.05)。结论外周血CD8+T细胞、CD4/CD8比值、NLR及PLR水平是影响老年NSCLC预后的独立影响因素,可作为评估老年NSCLC患者化疗预后的简易生物标志物。     

Enumeration of T lymphocyte subsets by monoclonal antibodies in young and aged humans

The percentage and absolute number of peripheral blood mononuclear cells reactive with monoclonal antibodies identifying mature thymocytes and T cells (T3+), helper/inducer cells (T4+), and suppressor/cytotoxic cells (T8+) was determined in 19 young (mean age 35 yr) and 31 elderly (mean age 72 yr) individuals. The percent representation but not the absolute number of T cells (T3+) declined significantly (p less than 0.001) in the elderly, and the decline was attributable to both an absolute and relative decrease in the representation of the subpopulation of cytotoxic/suppressor (T8+) cells. The percentage and number of helper/inducer (T4+) T cells was comparable in both age groups.     

Circulating immature and mature dendritic cells in relation to lymphocyte subsets in patients with gastrointestinal tract cancer

Cancer-related deficiency in circulating dendritic cells (DC), whose important anticancer role is well established, has been proven to be associated with lymphocytopenia. This study was performed to evaluate which lymphocyte subset is most markedly related to the failure of the DC system. The study included 30 patients with gastrointestinal tract cancer, 10 of whom had distant organ metastases. Immature and mature DCs were measured by FACS and monoclonal antibodies against CD123 and CD11c antigens, respectively. Low levels of immature and mature DCs were observed in 63% and 43% of patients, respectively. Patients with low levels of circulating mature DCs had significantly lower values of T lymphocytes, T helper lymphocytes and NK cells than those with normal mature DC levels. In contrast, no significant difference was seen between patients with normal or abnormally low values of immature DCs. Conversely, patients with a decreased number of T lymphocytes, T helper lymphocytes and NK cells showed significantly lower values of circulating mature DCs than those with lymphocyte subsets within the normal range, whereas no difference was seen in immature DC amounts. This study suggests that only mature DC deficiency may be associated with important lymphocyte subset alterations in cancer patients, whereas deficiency in immature DCs does not seem to be related to other immune cell disorders.