Gamma delta T lymphocytes in human tuberculosis.

The manifestations of tuberculous infection reflect the immune response to infection. Most healthy tuberculin reactors develop protective immunity; tuberculous pleuritis reflects a resistant response manifest by mild disease, whereas advanced pulmonary and miliary tuberculosis reflect ineffective immunity. The role of gamma delta T cells was assessed in tuberculous infection by evaluating expansion of these cells from blood mononuclear cells after stimulation with Mycobacterium tuberculosis. After culture in vitro, the percentages of gamma delta+ cells were significantly greater in patients with protective and resistant immunity (tuberculin reactors, 25% +/- 4%; tuberculous pleuritis, 30% +/- 7%) than in those with ineffective immunity (advanced pulmonary tuberculosis, 9% +/- 3%; miliary tuberculosis, 2% +/- 1%). In leprosy, expansion of gamma delta+ cells was greater in immunologically resistant tuberculoid patients (32% +/- 4%) than in Mycobacterium leprae-unresponsive lepromatous patients (9% +/- 2%). M. tuberculosis-reactive gamma delta T cell lines produced interferon-gamma, granulocyte-macrophage colony-stimulating factor, interleukin-3, and tumor necrosis factor-alpha, cytokines that activate macrophages and may contribute to mycobacterial elimination. These findings suggest that gamma delta T cells contribute to immune resistance against M. tuberculosis.     

白细胞介素12对结核病患者TH1/TH2平衡的影响

目的探讨白细胞介素12(IL-12)对结核病患者外周血单个核细胞(PBMC)分泌干扰素γ(IFN-γ)、白细胞介素4(IL-4)的影响.方法随机将25例结核患者和15名健康人PBMC分为RPMI1 640组、PPD组、PPD+rhIL-12组、PPD+anti-IL-12组,采用ELISA法检测各组培养上清液中IFN-γ、IL-4的水平.结果与PPD组相比,加入rhIL-12能有效增加结核患者及健康人PBMC分泌IFN-γ(分别为321.6±87.7至452.5±111.4, 387.0±70.8至515.4±44.1), 减少IL-4的分泌(54.6±11.0至41.3±13.5,55.1±9.5至38.2±12.7);而加入anti-IL-12可抑制IFN-γ的分泌,促进IL-4合成,且结核患者各组IFN-γ水平均低于健康人各对应组,而IL-4水平无差异.复治组IFN-γ、IL-4水平均低于初治组(P<0.05).结论 IL-12通过诱导IFN-γ分泌,抑制IL-4合成,从而调节TH1/TH2平衡,对结核分支杆菌感染患者产生保护性的免疫反应.IL-12可作为结核免疫调节剂,并可用于开发结核新疫苗.     

Potentiation of the macrophage 25-hydroxyvitamin D-1-hydroxylation reaction by human tuberculous pleural effusion fluid

1,25-Dihydroxyvitamin D [1,25-(OH)2D] is classically viewed as a steroid hormone of renal origin that regulates mammalian and avian mineral ion homeostasis. More recently, 1,25-(OH)2D has been shown to be produced by and act on human inflammatory cells in vitro, suggesting that the hormone may be an important modulator of the host immune response. We have recently detected high concentrations of 1,25-(OH)2D in the pleural fluid (PF) of patients with tuberculous pleuritis. Working on the hypothesis that tuberculous PF contained a soluble cytokine which stimulated 1,25-(OH)2D production by tissue (pleura)-based macrophages, we examined the potential for PF from five patients with tuberculous pleuritis to potentiate 1,25-(OH)2D synthesis by heterologous pulmonary alveolar macrophages (PAM) from patients with sarcoidosis; PAM from patients with active pulmonary sarcoidosis constitutively express a 25-hydroxyvitamin D3-1-hydroxylation reaction in vitro. We demonstrated that tuberculous PF had a concentration-dependent potentiating effect on PAM 1,25-(OH)2D synthesis. The potentiating activity was positively correlated to the interferon-gamma (IFN gamma) concentration of the PF (r = 0.98; P less than 0.01) and was inhibited by 49-89% after coincubation with anti-IFN gamma monoclonal antibody (1:20,000-1:200 dilution). These data suggest that IFN gamma may be an important peripleural regulator of macrophage 1,25-(OH)2D synthesis in patients with tuberculous pleuritis and a high pleural fluid 1,25-(OH)2D concentration.     

Specific in Vitro Proliferative Immune Responses and Lymphokine Production in Ethiopian Children with and without Tuberculosis

Summary We investigated the profile of some in vitro parameters of cellular immune responses in non-HIV-infected Ethiopian children and young adults with and without tuberculosis (TB) as compared to healthy Ethiopian and non-Ethiopian controls. The in vitro proliferative responses of peripheral blood mononuclear cells (PBMC) to purified protein derivative (PPD) were determined in 15 Ethiopian children and young adults with TB, 12 healthy Ethiopian children who were contacts of TB patients, 20 Ethiopian children without contact with TB and ten non-Ethiopian controls. All TB patients and contacts had a positive Mantoux skin test. The PBMC proliverative response to PPD of the Ethiopian children with TB was significantly higher than that of the Ethiopian children without TB, while all Ethiopian children demonstrated stronger proliferative response as compared to non-Ethiopian healthy controls. Interleukin 2 (IL-2), interferon gamma (IFN-γ), interleukin 4 (IL-4) and interleukin 6 (IL-6) were measured by ELISA assays performed on the supernatant of PPD-stimulated and non-stimulated PBMC cultures of seven Ethiopian children with TB, ten Ethiopian children without TB and eight non-Ethiopian controls. IFN-γ and IL-4 were undetectable and IL-2 levels in unstimulated supernatants were low in all groups. PPD stimulation induced a significant rise in IL-2 levels in Ethiopians with TB as compared to all other groups. There was no increase above baseline in IL-6 levels in any group studied. Conclusions: Ethiopian children with TB exhibit a strong cellular immune response as expressed by Mantoux tests and lack of stimulation of IL-4 and IL-6 production. This pattern suggests a Th1 type effective cellular immune response to mycobacteria in a cohort of young Ethiopians with TB. Received: December 3, 1998 · Revision accepted: December 4, 1999     

Tuberculous meningitis and miliary tuberculosis in young children

OBJECTIVES: To document the clinical and diagnostic features of tuberculous meningitis (TBM) in young children with and without concomitant miliary tuberculosis (TB). METHODS: A retrospective comparative study. RESULTS: Of 104 children with TBM, 32 (31%), median age 17.0 months, had a miliary appearance on chest radiograph; 72 (69%), median age 30.5 months, had TBM only (P = 0.04). Mediastinal adenopathy was noted in 27 (84%) of the children with miliary TB and 33 (46%) of those with TBM only (P = 0.0005). The mean cerebrospinal fluid (CSF) lymphocyte and polymorphonuclear counts of all children (no significant differences between groups) were 137 x 10(6)/l and 38 x 10(6)/l and the mean protein and glucose concentrations were 1.45 g/l and 0.72 mmol/l, respectively. Polymorphonuclear leukocytes were predominant in the CSF of 17% of children, in 16% the CSF glucose was > 2.2 mmol/l and in 26% the CSF protein was < 0.8 g/l. On Mantoux testing 37 (65%) of 57 children with TBM only and 12 (48%) of 25 children with TBM and miliary TB had an induration of > or = 10 mm (P = 0.23). Ten children (10%) died, five (7%) who had TBM only and five (16%) who had TBM and miliary TB. CONCLUSION: Children with TBM and miliary TB were younger and more likely to have mediastinal adenopathy on chest radiography than those with TBM only. Diagnostic features and investigations in both groups may be misleading at times.     

Relationship between disease duration and predominant orbital T cell subset in Graves' ophthalmopathy

We sought to determine whether the predominant orbital T helper (T(H)) cell subset in orbital T cell clones established from patients with Graves' ophthalmopathy (GO) might be related to disease duration. A total of 117 clones were established from orbital adipose/connective tissues of 6 GO patients, and cytokine production was measured in 57 CD3+CD4+ clones. T(H)1-type clones were predominant in cultures from patients with recent onset (<2 yr) Graves' hyperthyroidism (n = 44; TH1/TH0/TH2 = 57/29/14%) or GO (n = 53 clones; TH1/TH0/TH2 = 47/30/23%). In contrast, TH2-type clones predominated in cultures from patients with more remote onset (>2 yr) hyperthyroidism (n = 13; TH1/TH0/TH2 = 0/31/69%; P < 0.005) or GO (n = 4; TH1/TH0/TH2 = 0/25/75%; P = 0.05). In addition, we established T cell clones from 1 TH1-dominant patient with recent-onset thyroid and eye disease using either IL-2 (12.5 ng/mL) alone or IL-2 plus IL-4 (5 ng/mL) and found no shift toward recovery of TH2-type clones in the latter. In conclusion, although the CD3+CD4+ clones characterized were not necessarily tissue antigen specific, our findings suggest that cell-mediated (TH1-type) immune reactions may predominate in the orbit in early GO, whereas humoral immunity (TH2-type) might play the greater role in later stages of the disease.     

Correlation of tuberculin skin reaction with lymphocyte proliferation, interferon-gamma production and tumor necrosis factor-alpha production after in vitro stimulation with PPD and killed Mycobacterium tuberculosis using peripheral blood of healthy donors]

The quantitative relationships among the in vitro lymphocyte proliferation in peripheral blood in 19 healthy donors to purified protein derivative (PPD) and the killed Mycobacterium tuberculosis, interferon-gamma (IFN gamma) and tumor necrosis factor-alpha (TNF alpha) production in these culture supernatants, and the in vivo skin reaction to PPD which were simultaneously measured were studied. Statistical analysis was performed with t-test and multiple regression analysis: The results obtained were as follows; 1) The magnitude of the in vitro lymphocyte proliferation by PPD and the killed M. tuberculosis failed to correlate with the erythema and the induration of the in vivo skin reaction to PPD. 2) The erythema of skin test correlates with TNF alpha production in the culture supernatants that the lymphocytes in peripheral blood were cocultured with these antigens for 7 days. (R = 0.566062, 0.01 less than p less than 0.02) 3) There is a correlation between the erythema and the induration of skin test. (R = 0.526662, 0.02 less than p less than 0.05). 4) Though the magnitude of the lymphocyte proliferation to PPD correlates IFN gamma production in the culture supernatants (R = 0.525915, 0.02 less than p less than 0.05), these response to the killed M. tuberculosis correlates both IFN gamma production (R = 0.55049, 0.01 less than p less than 0.02) and TNF alpha production (R = 0.51283, 0.02 less than p less than 0.05) in the culture supernatants.(ABSTRACT TRUNCATED AT 250 WORDS)     

结核感染T细胞斑点试验在结核病诊断中的应用价值

目的 评价结核感染T细胞斑点试验(T-SPOT.TB)在结核病诊断及鉴别结核病是否为活动性方面的价值。 方法 回顾性分析2011年7月至2012年4月内蒙古医科大学附属医院587例住院患者（结核性疾病患者128例,其中活动性结核组103例,陈旧性结核组25例;非结核性疾病患者459例,免疫损害组241例,非免疫损害组218例）的年龄、性别、病程、临床表现、T-SPOT.TB、病理、PPD、抗酸杆菌涂片及Mtb-Ab等的结果,数据采用SPSS 16.0 软件处理,计量资料比较采用Wilcoxon秩和检验,计数资料采用卡方检验,以P<0.05为差异有统计学意义。 结果 187例T-SPOT.TB阳性者中确诊结核病患者106例,阳性预测值56.68%（106/187）,400例阴性者中确诊非结核病患者378例,阴性预测值 94.50%(378/400)。587例中共确诊结核性疾病128例,T-SPOT.TB检测的敏感度为82.81%（106/128）,均高于结核菌素纯蛋白衍化物（PPD）35.71%（30/84）、抗酸杆菌涂片8.74%（9/103）及结核抗体(Mtb-Ab)14.06%（9/64）的敏感度,活动性与陈旧性结核的检测敏感度分别为93.20%（96/103)和40.00% (10/25);459例非结核性疾病患者中免疫损害组与非免疫损害组T-SPOT.TB的检测特异度分别为71.37%（172/241）和94.50%(206/218)。结核性胸膜炎及腹膜炎患者T-SPOT.TB的敏感度为100.00%（37/37）。活动性结核与陈旧性结核病患者混合肽ESAT-6和CFP-10总SFCs计数中位数分别为502个/10⁶ PBMCs和430个/10⁶ PBMCs, 四分位数间距（P₂₅, P₇₅）分别为(217个/10⁶ PBMCs,1287个/10⁶ PBMCs)和(140个/10⁶ PBMCs,1303个/10⁶ PBMCs),两组间比较采用Wilcoxon秩和检验,差异无统计学意义（U=429.5,P=0.585）。肺结核与肺外结核患者混合肽ESAT-6和CFP-10总SFC中位数分别为456个/10⁶ PBMCs和528个/10⁶ PBMCs, 四分位数间距（P₂₅, P₇₅）分别为(264个/10⁶ PBMCs,950个/10⁶ PBMCs)和(186个/10⁶ PBMCs,1244个/10⁶ PBMCs),两组间差异无统计学意义（U=1083.0,P=0.871）。 结论 T-SPOT.TB在低风险人群中检测的特异度较好,而在有潜在结核分枝杆菌感染的高危人群中检测的特异度明显降低,在结核性浆膜腔积液中检测的敏感度较高,与PPD、抗酸杆菌涂片及Mtb-Ab相比,敏感度较高,但对鉴别是否为活动性结核病并不理想。     

Increased pulmonary gamma interferon production in asbestosis

In order to determine if disordered cellular immune processes are present in the lungs of persons with asbestosis, we performed bronchoalveolar lavage (BAL) on 26 patients with either crocidolite- or chrysotile-induced pulmonary asbestosis and measured the spontaneous release of gamma interferon (IFN gamma), a marker of increased cellular immune activity. For comparison, 18 control subjects and 7 patients with active pulmonary sarcoidosis were also studied. Recovered BAL cells were cultured for 24 h (5 x 10(6)/ml), and the supernatant was assayed for interferon by determining inhibition of cytopathic effect on encephalomyocarditis virus-induced lysis of WISH cells and characterized by monoclonal anti-IFN gamma antibody inhibition. Nine (35%) patients with asbestosis released increased amounts of IFN gamma, up to 320 units/ml, the levels seen in the sarcoidosis patients. All control subjects released less than or equal to 10 units/ml. All interferon released was IFN gamma. In asbestosis patients, IFN gamma production was not related to a history of cigarette smoking, there was no significant difference in the ratio of helper/inducer (Leu-3) to suppressor/cytotoxic (Leu-2) cells in IFN gamma producers compared to non-IFN gamma producers (p greater than 0.05), and IFN gamma production correlated significantly with serum IgG levels (p less than 0.001) but not with the levels of IgM, IgA, antinuclear factor, or rheumatoid factor. These data suggest that active cellular immune processes are present in the lungs of a proportion of patients with asbestosis.     

Mycobacterium tuberculosis infection in patients with systemic rheumatic diseases. A case-series.

OBJECTIVE: To describe the clinical characteristics of patients with systemic rheumatic diseases and tuberculosis. A retrospective case series from 1987 to 1994, drawn from a tertiary-care hospital in Mexico City, was studied. RESULTS: Thirty patients were included (20 women, 10 men), with mean age of 39.8 years (range 14-66), and a mean duration of the systemic rheumatic disease of 44 months (1-372). The rheumatic diseases included systemic lupus erythematosus (SLE) (n = 13), rheumatoid arthritis (7), polymyositis or dermatomyositis (5), and other diseases (5). During the six months previous to the diagnosis of tuberculosis, 22 patients had received corticosteroids, and 13 others immunosuppressants. Mycobacterium tuberculosis was isolated from 18 patients. Pulmonary tuberculosis was found in 10 patients, and extrapulmonary tuberculosis in 20, seven of these with miliary disease. SLE was seen in 6 of the patients with miliary tuberculosis. The clinical manifestations were: fever (67%), weight loss (67%), diaphoresis (60%), cough and sputum (53%), lymph node enlargement (43%), and dyspnea (33%). Sixteen patients had an abnormal chest film. Of 18 patients tested by PPD RT-2, 8 had an induration > 10 mm. Patients were initially treated with 3 or 4 anti-tuberculosis drugs for 15 days to 6 months, followed by 6 to 10 months of isoniazid plus rifampicin. Three relapsed, and 2 died of respiratory failure. CONCLUSIONS: This case series showed a particular pattern of tuberculosis in patients with systemic rheumatic diseases.     

Skin anergy and tuberculosis.

In our experience tuberculin skin anergy (negative response to 10 TU Mantoux) occurs in 8% of patients with tuberculosis. In this study we compare 81 patients with skin anergy and proven tuberculosis with a background reactive population of patients with tuberculosis. Patients with skin anergy and tuberculosis were older and had fewer symptoms--less cough, less sputum production, less haemoptysis, less malaise, less chest pain--than patients with skin reactivity. There was no difference with respect to male/female ratio, marital status, smoking habits, coexistent major illness, prescribed medications at diagnosis, nor the proportion of patients with extrapulmonary tuberculosis, previous history of BCG vaccination or past history of tuberculosis. Comparison of chest radiographs showed more advanced, more bilateral and more miliary disease in the anergic patients. Pyrexia and elevated ESR at diagnosis were also more common in this group. Fewer of the anergic group of patients were consistently culture negative after 1 month's treatment compared to the background population. Mortality was higher in the anergic group, but this excess mortality occurred from causes other than tuberculosis. Repeat Mantoux testing was performed in 20 of the 81 anergic patients, after a minimum of 3 months of antituberculous chemotherapy, and 14 had become tuberculin positive, suggesting that tuberculin skin anergy may be a temporary phenomenon.     

Lymphocyte subpopulations of blood and alveolar lavage in blastomycosis

Patients with blastomycosis were found to have differing lymphocyte populations depending on the extent of disease manifestations and whether or not therapy had been started. Patients with recovering pulmonary blastomycosis who had been receiving antifungal treatment for at least four weeks had lymphocyte subpopulations no different from control donors. Patients with treated extrapulmonary blastomycosis had similar T helper (TH) to T suppressor (TS) ratios compared to recovering pulmonary patients and control subjects; this ratio gives a false impression because extrapulmonary blastomycosis patients had a reduced absolute number of lymphocytes with either marker. In bronchoalveolar lavage fluid, pulmonary blastomycosis patients who were clinically improved while receiving antifungal therapy had fewer TH cells and a greater number of lymphocytes with the TS marker than did control subjects. Patients with pulmonary blastomycosis prior to therapy had a smaller TH/S ratio than the other groups in peripheral blood primarily due to a reduction in the circulating TH fraction in both absolute numbers of cells and in the percentage of total T lymphocytes. Pulmonary blastomycosis patients re-evaluated after at least four weeks of antifungal therapy had TH/S ratios that were similar to normal persons. This increase in TH lymphocytes corresponded to clinical improvement and in a temporal correlation to that described for the development of specific immunity in this illness.     

High level of interferon gamma in tuberculous pleural effusion

It has been observed that T-lymphocytes of patients with tuberculosis produce interferon gamma (IFN gamma) in vitro. Based on this idea, we studied IFN gamma in pleural fluid and serum. We studied 80 patients with pleural effusion; 30 patients with tuberculous pleurisy had high IFN gamma concentrations in pleural fluid. Patients with malignant pleural effusions, nonspecific pleural effusion, parapneumonic effusions and pleural transudates had low levels. The IFN gamma levels were higher in those with massive tuberculous effusion and apparent pulmonary lesion on x-ray film. We found that the T4/T8 lymphocyte ratio was higher in pleural fluid than in peripheral blood. Numbers of T3 and T4 lymphocytes were higher in tuberculous pleural effusions compared with those in other patients. There is no correlation between IFN gamma levels and lymphocyte subsets in pleural effusion. Perhaps pleural T-lymphocytes produce IFN gamma after stimulation by mycobacterial antigens and this lymphokine activates macrophages, increasing their bactericidal activity against Mycobacterium tuberculosis.     

Modulation of helper T cell function by prostaglandins

Objective. To determine the influence of prostaglandins on the production of interleukins 2, 4, and 5 (IL-2, IL-4, and IL-5), interferon-γ (IFNγ), granulocytemacrophage colony-stimulating factor, and transforming growth factor β1 by CD4+ T cells. Methods. TH0, TH1, and TH2 T cell clones were stimulated in the presence and absence of the prostaglandin E₁ (PGE₁) analog misoprostol and PGE₂. Lymphokine production was analyzed by using a semiquantitative polymerase chain reaction with lymphokine-specific primer sets and/or by determining lymphokine activity in bioassays. Results. PGE₂ and misoprostol have distinct effects on different functional T helper cells. TH1 cells, which predominantly produce IL-2 and IFNγ, are completely inhibited, while TH2 cells, which preferentially produce IL-4 and IL-5, are largely unaffected. Misoprostol and PGE₂ are equivalent in their ability to modulate T cell function. In the presence of prostaglandins, THO-like helper cells, which are characterized by the coproduction of multiple lymphokines, function as TH2 cells; however, they do not differentiate into TH2 T cells. Conclusion. Prostaglandins that are produced in inflamed tissue can regulate the functional capabilities of infiltrating T cells. In the presence of PGE₂, TH1-like responses are suppressed and TH0-like responses are shifted toward a TH2-like pattern dominated by the production of IL-4 and IL-5. Inhibition of prostaglandin production by antiinflammatory agents might restore TH1 responses with local production of IL-2 and IFNγ.     

Antimycobacterial immune responses in patients with pulmonary sarcoidosis

Introduction: Sarcoidosis is a multisystem granulomatous disease of unknown origin. Pathogenetic involvement of Mycobacterium tuberculosis has frequently been discussed in the aetiology of sarcoidosis; however, studies still remain contradictory. Objective: We addressed the question of mycobacterial involvement in the pathogenesis of sarcoidosis by analysing cellular immune responses to mycobacterial antigens. Methods: We examined the interferon (IFN)‐γ production by enzyme‐linked immunospot in response to purified protein derivate (PPD) mycobacterial‐specific antigen early secretory antigenic target (ESAT)‐6 and culture filtrate protein (CFP)‐10 by peripheral blood mononuclear cells (PBMCs) and bronchoalveolar‐lavage mononuclear cells (BALMCs) of patients with pulmonary sarcoidosis, smear‐negative tuberculosis and controls. Results: Release of IFN‐γ in response to ex vivo contact with PPD, ESAT‐6 or CFP‐10 by BALMC and PBMC were comparable among patients with sarcoidosis and controls (PBMC P = 0.2326; BALMC P = 0.1767) and were less frequently observed in both groups compared to patients with tuberculosis (BALMC P < 0.05; PBMC P < 0.0001). Within PBMC, the immunophenotype of sarcoidosis patients differed from that of patients with tuberculosis, as well as from that of controls, while within BALMC it resembled that of patients with tuberculosis. Conclusion: In contrast to patients with tuberculosis, the frequency of mycobacteria‐specific local and systemic immune responses is not elevated in patients with sarcoidosis when compared to controls. The immunophenotype represents the local resemblance of the granulomatous reaction underlying tuberculosis and sarcoidosis while showing systemical difference. These observations do not support a role of an infection with M. tuberculosis in the pathogenesis of sarcoidosis. Please cite this paper as: Hörster R, Kirsten D, Gaede KI, Jafari C, Strassburg A, Greinert U, Kalsdorf B, Ernst M and Lange C. Antimycobacterial immune responses in patients with pulmonary sarcoidosis. The Clinical Respiratory Journal 2009; 3: 229–238.     

Lymphocyte proliferation and gamma-interferon production after "in vitro" stimulation with PPD. Differences between tuberculous and nontuberculous pleurisy in patients with positive tuberculin skin test

T-lymphocytes previously sensitized by an antigen undergo blastic transformation and produce IFN tau when stimulated by the same antigen. We studied the lymphoblastic response to PPD and IFN tau production in pleural fluid and peripheral blood of 41 patients (15 with tuberculous pleural effusion, 13 with nontuberculous pleurisy and positive tuberculin skin test, and 13 with tuberculin-negative nontuberculous pleurisy). In tuberculous pleuritis, pleural lymphocyte blastic response and IFN tau production were higher than those of peripheral lymphocytes, whereas in tuberculin-positive nontuberculous patients, peripheral lymphocyte response and IFN tau production were higher than those of pleural lymphocytes. Tuberculous pleural fluid lymphocytes underwent greater blastic transformation and produced more IFN tau than pleural lymphocytes of tuberculin-positive nontuberculous patients, whereas the opposite occurred in peripheral lymphocytes. In tuberculin-negative nontuberculous patients, there was no lymphoblastic response in either the pleural fluid or peripheral blood. These results concur with the concept of immunologic compartmentalization. In tuberculous pleuritis, there would be clonal expansion of PPD-responding T-lymphocytes in the pleural compartment. This expansion of PPD-specific lymphocytes would not occur in nontuberculous pleuritis, but lymphocytes sensitized to other antigens would accumulate in the pleural compartment.     

Decreased production of interferon gamma by anti-CD3 monoclonal antibody and interleukin-2 -stimulated peripheral blood mononuclear cells in Hodgkin's disease

Summary. We have examined the production of interferon (IFN) gamma by peripheral blood mononuclear cells (PBMC) in 22 patients with Hodgkin's disease (HD) in active phase of the disease, 12 patients in clinical remission and 16 healthy subjects. The level of IFN gamma in supernatants of PBMC stimulated for 72 h with anti-CD3 monoclonal antibody (mAb), measured by sandwich enzyme immunoassay (ELISA) was 50.4 ± 2.3 U/ml in active phase; 137.0 ±7.4 U/ml in clinical remission patients; and 520.0 ± 10.0 U/ml in the controls; the difference between the groups was statistically significant. Co-stimulation with interleukin-2 (rIL-2) markedly amplified production of IFN gamma. The mean levels were 220.8 ±7.0U/ml, 590-7 ±3-6U/ml and 2111.1 ± 17.3 U/ml in active phase HD, clinical remission and controls, respectively, the difference between groups was statistically significant. The patients showed the same kinetic pattern as healthy individuals. Our results indicate that patients with HD have severely impaired TCR/CD3 activation pathway resulting in significantly depressed IFN gamma response to anti-CD3 mAb and anti-CD3 + rIL-2 in vitro stimulation and provide support for the possible clinical use of IFN gamma as an immunopotentiating agent in patients with HD.     

胸液γ-干扰素和α-肿瘤坏死因子检测对结核性胸膜炎诊断价值的探讨

目的检测结核性胸膜炎及恶性胸膜炎患者血清与胸液的γ-干扰素和α-肿瘤坏死因子水平,探讨对结核性胸膜炎诊断的临床价值?方法采用酶联免疫吸附法(ELISA)检测41例结核性胸膜炎?40例恶性胸膜炎患者血清及胸液和41例健康对照组血清的γ-干扰素和α-肿瘤坏死因子水平?结果结核性胸膜炎患者两者含量(427.3±56.8?184.7±64.7pg/ml)明显高于恶性胸膜炎组(45.6±20.3?50.5±18.7)(P<0.01),且重叠性很小;而两组血清含量很低并相近,与健康对照组比较无显著差异(P>0.05)?γ-干拢素和α-肿瘤坏死因子作为诊断结核性胸膜炎的敏感性?特异性?准确性分别为100.0%?97.5%?98.8%及87.8%?90.0%?88.9%?结论检测胸液γ-干扰素和α-肿瘤坏死因子对诊断结核性胸膜炎有较大的辅助意义?     

Nontoxic nodular goiter and papillary thyroid carcinoma are not associated with peripheral blood lymphocyte sensitization to thyroid cells

We tested the claim that uni- and multinodular goiter (UNG and MNG) and papillary carcinoma (PC) of the thyroid are autoimmune thyroid diseases (AITD) similar to Graves' disease (GD) and Hashimoto's thyroiditis (HT). The expression of HLA-DR on cultured thyroid epithelial cells (thyrocytes) from UNG, MNG, and PC after coculture with autologous peripheral blood mononuclear cells (PBMC) was compared with that on GD and HT cells. The thyrocytes also were cultured with interferon-gamma (IFN gamma) alone. A cytotoxicity assay involving 51Cr-labeled thyrocytes, anti-HLA-DR, and complement was used to determine HLA-DR expression. Stimulation of thyrocytes with 200 U/mL IFN gamma induced HLA-DR (expressed as a cytotoxicity index) equally well on all thyrocytes [AITD (n = 6): IFN gamma, 23.8 +/- 7.7 (+/- SD); unstimulated, 3.6 +/- 2.0; UNG (n = 6), MNG (n = 9), and PC (n = 5): IFN gamma, 22.5 +/- 4.7; unstimulated, 4.0 +/- 3.0]. When cocultured with autologous PBMC, the values were: AITD, 24.9 +/- 10.1; UNG, MNG, and PC, 3.8 +/- 3.7 (P less than 0.001). The supernatants from the AITD cocultures had higher IFN gamma concentrations (by RIA) than those from the other cocultures. We conclude that in UNG, MNG, and PC, the peripheral blood helper T-lymphocytes are not sensitized to thyrocyte membrane antigen(s); consequently, little if any IFN gamma is produced in cocultures, and hence, there is no increase in thyrocyte HLA-DR expression, unlike the situation in AITD (GD and HT). Thus, UNG, MNG, and PC are not primarily autoimmune in nature, as defined by a lack of sensitization of the PBMC of such patients to thyroid antigen(s).