肿瘤患者胸/腹水和外周血中TCR Vβ亚家族表达及调节性T细胞亚群的研究

目的:探讨肿瘤患者胸/腹水中肿瘤浸润性淋巴细胞(TIL)和外周血T细胞中T细胞受体(TCR)Vβ亚家族的表达变化情况、CD4/CD8细胞比例变化和Treg细胞的分布情况,分析肿瘤患者的免疫状态。方法:分离11例肿瘤患者胸/腹水和外周血以及4例健康人外周血的T细胞,采用流式方法检测Vβ24个亚家族及CD3、CD4、CD8、CD25、CD127的表达情况,统计分析T细胞中Vβ24个亚家族、Treg细胞的特点。结果:TCR Vβ亚家族的表达在肿瘤患者胸/腹水TIL中与血液淋巴细胞中存在着显著差异,其中肺癌患者(4/5)TIL中TCR Vβ8,结肠癌患者(3/4)TIL中TCR Vβ2等亚家族显著高表达;11例肿瘤患者胸/腹水样本中Treg的比例均比外周血高(P<0.05),其中5例肺癌患者胸腹水中CD8+T细胞比例降低。结论:肿瘤患者胸/腹水中的淋巴细胞TCR Vβ亚家族表达与外周血存在差异,表明肿瘤患者体内淋巴细胞发生了明显的优势取用和定向趋化。此外肿瘤微环境可能影响了TIL中CD4+细胞的分化导致胸腹水中Treg细胞的比例升高,同时伴随着CD8+T比例的下降,并可能因此影响到TIL中TCR Vβ亚家族的优势取用情况,且导致免疫耐受。     

T-cell differentiation antigens and antigenic lymphocyte reactivity in pleural effusions

Blood and pleural effusion mononuclear cells from thirteen patients were examined for the expression of T lymphocyte differentiation antigens as well as in vitro thymidine incorporation. The ratio of T4 to T8 cells was significantly greater among pleural effusion lymphocytes than among blood lymphocytes. Effusion lymphocyte responses to phytohaemagglutinin were less than those of blood lymphocytes. Unstimulated thymidine incorporation was greater in pleural effusion lymphocytes. Antigen-stimulated lymphocyte reactivity was not consistently greater in either blood or effusion lymphocytes. Lymphocytes from tuberculous effusions all reacted to tuberculin. Pleural effusion lymphocytes, regardless of the etiology of the effusion, possessed the same range of antigenic specificities as did blood lymphocytes. Therefore, effusion lymphocyte responsiveness to tuberculin does not prove the presence of tuberculous pleurisy but does indicate sensitisation to tuberculin.     

Analysis of T cell subsets by monoclonal antibodies in patients with tuberculosis after in vitro stimulation with purified protein derivative of tuberculin.

By using OKT monoclonal antibodies; OKT3(pan T), OKT4(inducer/helper), OKT8 (suppressor/cytotoxic) and OKIa1, T lymphocyte subsets were examined in lymphocytes of patients with tuberculosis both before and after in vitro stimulation with purified protein derivative of tuberculin (PPD). In freshly obtained lymphocytes samples before culture, a significantly high T4/T8 ratio in pleural fluid lymphocytes (PFL) from patients with tuberculous pleurisy was observed as compared with either their PBL, or the PBL from healthy controls. In addition, PFL from patients with tuberculous pleurisy showed increased numbers of E rosetting (E-RFC), OKT3+ and OKT4+ cells as compared with their PBL. A low T4/T8 ratio was also observed in PBL of patients with advanced, refractory tuberculosis. After stimulation with PPD in vitro, the T4/T8 ratio increased further in PFL as well as in PBL from patients with newly diagnosed, fresh tuberculosis. Investigation of fractionated T lymphocyte subsets revealed that PPD-induced proliferating lymphocytes belonged to T4+ and not T8+ lymphocytes. Ia antigen bearing T lymphocytes (Ia-T) were increased in all lymphocyte groups studied after in vitro stimulation with PPD. In particular, a remarkable increase was observed when PFL were stimulated in vitro with PPD. Our results suggest that the clinical features of tuberculosis reflect the immunological activity of T lymphocyte subsets in this disease.     

Crucial Role of CD4+CD 25+ FOXP3+ T Regulatory Cell,Interferon-γ and Interleukin-16 in Malignant and Tuberculous Pleural Effusions

The differential diagnosis between malignant and tuberculous exudative pleural effusions is an important clinical problem. The aim of current study is to evaluate the frequencies of T-regulatory cells (Treg) on the basis of distinct phenotypes in the differential diagnosis between malignant and tuberculous pleural effusion. In addition, to evaluate Interferon-gamma (IFN- γ) and interleukin-16 (IL-16) levels and their correlation to Treg cells in malignant and tuberculous pleural effusions. Sixty patients with pleural effusion (26 tuberculous and 34 malignant) and 20 healthy controls were included in the study. Pleural fluid and peripheral blood were assessed for frequencies of T regs, IL-16, and IFN-γ. Pleural effusions from both tuberculous and malignant groups represented significantly higher levels (more in TB) for the following cell populations than peripheral blood: total lymphocytes, CD3+lymphocyte, CD4+CD25+lymphocyte and Treg (CD4+ CD25+FoxP3+). Levels of IL-16 and IFN-γ in tuberculous group were significantly higher than that in malignant group. Regulatory T cells, INF-γ and IL-16 are new important tools for differentiation between tuberculous and malignant pleural effusion.     

Effect of neutralizing transforming growth factor beta1 on the immune response against Mycobacterium tuberculosis in guinea pigs

Transforming growth factor beta (TGF-beta) is a cytokine which has been shown to suppress the antimycobacterial immune responses of humans and experimental animals. In this study, the contributions of TGF-beta to cytokine production in vivo were investigated by using the established guinea pig model of tuberculous pleurisy. Mycobacterium bovis BCG-vaccinated guinea pigs were injected intrapleurally with heat-killed virulent Mycobacterium tuberculosis. Eight days following induction of an antigen-specific pleural effusion, guinea pigs were injected intrapleurally with anti-TGF-beta1 or isotype control antibody. The following day, pleural exudates were removed, and the fluid volume and characteristics of the infiltrating cells were determined. Pleural fluid was analyzed for total interferon (IFN) and tumor necrosis factor (TNF) protein levels by using appropriate bioassays. RNA from pleural effusion cells was examined to determine TGF-beta1, TNF-alpha, IFN-gamma, and interleukin-8 mRNA levels by using real-time PCR. Proliferative responses of pleural effusion lymphocytes were examined in response to concanavalin A and purified protein derivative (PPD) in vitro. Treatment with anti-TGF-beta1 resulted in decreased pleural fluid volume and decreased cell numbers in the pleural space along with an increased percentage of lymphocytes and a decreased percentage of neutrophils. The bioactive TNF protein levels in pleural fluid were increased in guinea pigs treated with anti-TGF-beta1, while the bioactive IFN protein concentrations were not altered. Expression of TGF-beta1 and TNF-alpha mRNA was significantly increased following TGF-beta1 neutralization. Finally, PPD-induced proliferative responses of pleural cells from anti-TGF-beta1-treated animals were significantly enhanced. Thus, TGF-beta1 may be involved in the resolution of this local, mycobacterial antigen-specific inflammatory response.     

Gamma Interferon Immunospot Assay of Pleural Effusion Mononuclear Cells for Diagnosis of Tuberculous Pleurisy

Diagnosis of tuberculous pleurisy remains a challenge in the clinic. In this study, we evaluated the usefulness of a previously developed Mycobacterium tuberculosis antigen-specific gamma interferon enzyme-linked immunospot (ELISPOT) assay in the diagnosis of tuberculous pleurisy by testing a cohort of 352 patients with pleural effusion. We found that M. tuberculosis antigen-specific gamma interferon-producing cells were enriched four to five times in pleural fluid compared with their levels in peripheral blood from patients with tuberuclous pleurisy assayed in parallel. The sensitivity, specificity, positive predictive value, and negative predictive value of the pleural fluid mononuclear cell ELISPOT assay for the diagnosis of tuberculous pleurisy were 95.7%, 100%, 100%, and 81.0%, respectively. In comparison, the sensitivity and specificity of the ELISPOT assay using peripheral blood mononuclear cells were 78.3% and 86.3%, respectively. The sensitivity and specificity of the pleural fluid adenosine deaminase activity test were 55.5% and 86.3%, respectively. These results demonstrate that the M. tuberculosis antigen-specific ELISPOT assay performed on pleural fluid mononuclear cells provides an accurate, rapid diagnosis of tuberculous pleurisy.     

Elevated IL-5 levels in pleural fluid of patients with paragonimiasis westermani

To investigate the pathogenic mechanisms of eosinophilic pleural effusion in patients with paragonimiasis, we measured the levels of IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma) in pleural effusions. Samples were obtained from 11 patients with Paragonimus westermani infection. In addition, samples from 12 patients with pleural transudates, 16 with tuberculous pleurisy, seven with empyema and 20 with lung cancer were also examined. Eosinophilia was remarkable in peripheral blood (range 4-34%, median 23.4%) and pleural fluid (range 0-95%, median 71%) of paragonimiasis patients. IL-5 concentrations in pleural effusions of paragonimiasis were markedly higher than those in other groups. Although marked elevation of GM-CSF and IFN-gamma levels was observed in pleural effusion of empyema and tuberculosis patients, it was marginal in the pleural effusion of paragonimiasis patients. In paragonimiasis patients, IL-5 levels in the pleural effusion correlated well with the percentage of eosinophils in peripheral blood and pleural fluid. Such a correlation was not observed between GM-CSF levels in pleural effusion and percentages of eosinophils in pleural fluid or peripheral blood. Our findings suggest that in paragonimiasis IL-5 in the local inflammatory site is particularly important in mediating eosinophilia in peripheral blood and pleural effusion.     

Purified protein derivative of tuberculin upregulates the expression of vascular endothelial growth factor in T lymphocytes in vitro

The purpose of this study was to investigate the cellular source and significance of vascular endothelial growth factor (VEGF) which, as reported previously, is elevated in the sera of pulmonary tuberculous patients. We obtained peripheral blood mononuclear cells (PBMCs) from 28 patients with active pulmonary tuberculosis, from 11 healthy controls who were positive for purified protein derivative of tuberculin (PPD), and from eight healthy individuals who were negative for PPD. We incubated the PBMCs with PPD in the presence or absence of major histocompatibility (MHC) class I or class II antibody in vitro, and measured the VEGF levels of culture supernatants. We also analysed the source of cells that secrete VEGF by using flow cytometry with intracellular staining. The T lymphocytes of active tuberculous patients secreted a higher level of VEGF than those of healthy controls. This production of VEGF was inhibited by adding MHC class II antibody. The addition of MHC class I antibody, however, did not inhibit. We propose that CD4+ T lymphocytes are almost certainly the cells that produce VEGF in response to PPD. VEGF production might be associated with an antigen-specific immune reaction via CD4+ T lymphocytes in tuberculosis.     

Tuberculous pleural effusions: lymphocyte phenotypes in comparison with other lymphocyte-rich effusions

This study investigated whether the analysis of T cell subsets and of activation markers on T cells in pleural fluids can be helpful for diagnostic purposes in tuberculous pleurisy and other lymphocyte-rich pleural effusions. Pleural effusion fluids were obtained from 18 patients with tuberculous pleurisy (TB), 21 with effusions following radiotherapy (RT) for a malignant disease, and 11 with congestive heart failure (CHF). Lymphocyte subsets were analyzed by a battery of monoclonal antibodies using an immunoperoxidase method. The majority of the lymphocytes were CD3-positive T cells (TB, 86 +/- 7% of lymphocytes; RT, 81 +/- 8%; CHF, 84 +/- 12%). The ratios of CD4-positive helper-inducer to CD8-positive suppressor-cytotoxic T cells were higher than those reported for the peripheral blood but not significantly different between the study groups (TB, 3.3 +/- 1.9; RT, 2.8 +/- 1.4; CHF, 2.5 +/- 1.1). The activation marker studies revealed that only a few pleural T cells were positive for CD38, CD25 (interleukin-2 receptor), HLA-DR antigen, and OKT9 (transferrin receptor), the proportion of CD25-positive T cells being higher in TB and in RT than in CHF and the proportion of HLA-DR-positive T cells being higher in TB than in CHF (P less than 0.05). Significant differences were not observed relative to the natural killer-cytotoxic phenotypes staining positive for Leu-7 or for CD16. Thus, we concluded that phenotypic analysis of lymphocytes is of limited diagnostic usefulness to differentiate tuberculous from other nonmalignant effusions.     

T-lymphocyte response in a guinea pig model of tuberculous pleuritis.

The ability to induce tuberculous pleuritis in Mycobacterium bovis BCG-vaccinated guinea pigs was investigated as a model of human disease. A pleural effusion of 5 to 10 ml was obtained 6 to 7 days after the bilateral pleural injection of a suspension of heat-killed M. tuberculosis cells. Histological lesions were indicative of granulomatous pleuritis. Comparative studies of T lymphocytes obtained from pleural fluid and peripheral blood revealed increased antigen-driven lymphoproliferation and E rosette formation in pleural effusion lymphocytes. The CD2+ T-lymphocyte population appeared to be expanded or concentrated in pleural fluid, suggesting a compartmentalization of antigen-reactive T lymphocytes. These data demonstrate that experimental tuberculous pleuritis with effusion, closely resembling the human disease, can be produced in BCG-vaccinated guinea pigs.     

Lymphocyte populations during tuberculosis infection: V beta repertoires.

The immune response to Mycobacterium tuberculosis is mediated by T lymphocytes. We studied the changes in lymphocyte populations occurring in peripheral blood, pleural fluid, and ascites during tuberculosis infection. For this purpose, we compared recent-onset patients (newly converted to positive Mantoux reactions) with previously diagnosed patients (individuals with organic lesions). Recent infection was associated with peripheral blood lymphocytosis involving T lymphocytes expressing either T-cell receptor alpha/beta or gamma/delta. Lymphocytosis involved both CD4 and CD8 cells. On the other hand, we detected no changes in the distribution of peripheral blood lymphocyte populations in previously diagnosed patients. No changes were found in the numbers of B lymphocytes or natural killer cells in either recently infected or previously diagnosed patients. The pleural effusion and ascitic fluid samples contained T lymphocytes expressing T-cell receptor alpha/beta, the majority of which were CD4+. These lymphocytes showed an inverted CD45RA-to-CD45RO ratio, and we found high-level expression of the interleukin-2 receptor (CD25) in some patients. The results are compatible with the existence of periods of cell activation in the pleural fluid (which are disclosed by the appearance of the CD25 antigen and the transition of CD45RA expression to CD45RO) together with nonactivation periods (loss of CD25 and persistence of CD45RO expression). We studied a fraction of the V beta repertoire in peripheral blood in both groups and the same fraction of the V beta repertoire in pleural fluid from patients with tuberculous pleuritis, demonstrating that, in recently infected subjects, lymphocytosis was produced by the increase in lymphocytes which expressed some specific V beta subfamilies that differed from one individual to another. In two of five patients studied, we found significant changes in the V beta repertoire between lymphocytes from peripheral blood and the pleural fluid samples.     

IL-18 production in human pulmonary and pleural tuberculosis

Interleukin-18 (IL-18) has multiple important pro-inflammatory effects, including the induction of interferon-gamma (IFN-gamma) in various diseases. In this study, we investigated the IL-18-producing activities in human pulmonary and pleural tuberculosis (TB) in response to purified protein derivative (PPD) antigen (Ag) from Mycobacterium tuberculosis. The most significant IL-18 production was found in chronic refractory TB (CRTB) patients. However, IFN-gamma production in CRTB patients was significantly less than that in healthy tuberculin reactors or in patients with tuberculous pleurisy (TBP). Elevated levels of both IL-18 and IFN-gamma were found in pleural fluids from TBP patients. In vitro production of IL-18 was dramatically decreased following an 18 h stimulation with PPD. However, IFN-gamma was markedly increased in pleural mononuclear cells from TBP patients after in vitro stimulation with PPD. The mesothelial cell type was the main source of pro-IL-18 in pleural cells from TBP patients, suggesting an important role for these cells in TBP. Taken together, these data indicate that IL-18 is elevated in peripheral blood mononuclear cells from CRTB patients, as well as at the site of TBP, indicating a possible role for IL-18 in both protective immunity and pathologic responses in human TB.     

Limiting dilution analysis of proliferative T cell responses to mycobacterial 65-kDa heat-shock protein fails to show significant frequency differences between synovial fluid and peripheral blood of patients with rheumatoid arthritis.

Recent evidence has pointed to the mycobacterial 65-kDa heat-shock protein (hsp 65) as an antigen that may be important in the pathogenesis of rheumatoid arthritis (RA). Using limiting dilution analysis the frequency of purified protein derivative of tuberculin (PPD) and hsp 65-responsive T cells was measured in paired peripheral blood and synovial fluid samples of patients with RA. There was no increase in the anti-PPD or anti-hsp 65 frequency in synovial fluid compared with peripheral blood. In addition, no difference was found between peripheral blood of RA patients and healthy controls. These results do not support the idea of an important pathogenic role of T cells responding to hsp 65, or a cross-reacting antigen, in RA.     

Anti-purified protein derivative cell-enzyme-linked immunosorbent assay, a sensitive method for early diagnosis of tuberculous meningitis.

A cell-enzyme-linked immunosorbent assay method was developed for the diagnosis of tuberculous meningitis by determining anti-purified protein derivative antibody production by cells derived from cerebrospinal fluid and peripheral blood. Of 20 patients with clinical histories and CSF findings suggestive of tuberculous meningitis, 18 showed high production of anti-purified protein derivative immunoglobulin antibody from CSF-derived lymphocytes, while none of the controls showed such response.     

Characterization of Active T Cells in CSF and Blood in Multiple Sclerosis Patients and Controls

In thirty-two patients with multiple sclerosis (MS), significantly lower percentages of active T cells--that is, lymphocytes which have been incubated at 37 degrees C for 1 h before 5 min rosetting with sheep erythrocytes--were found in cerebrospinal fluid (CSF) than in blood, whereas the reverse was observed in twenty of twenty-two patients with other neurological diseases (OND). No significant difference was found between percentages of active T cells in blood in MS, OND, and healthy controls. Lymphocytes from MS CSF are extensively temperature-labile when examined under different test conditions; without incubation at 37 degrees C for 1 h, active T cell percentages in CSF of both patients with MS and OND were, in fact, higher than in peripheral blood. The mitogen response patterns of enriched active T cells and unseparated lymphocytes from peripheral blood did not discriminate between patients with MS and healthy controls. Although active T cell values have been shown to correlate with cell-mediated immunocompetence, they have not yet been defined functionally. One of the explanations for the present findings could be that lymphocytes themselves in MS patients' CSF are at least partly virus-infected.     

T-cell responses to the Mycobacterium tuberculosis-specific antigen ESAT-6 in Brazilian tuberculosis patients

The Mycobacterium tuberculosis-specific ESAT-6 antigen induces highly potent T-cell responses and production of gamma interferon (IFN-gamma), which play a critical role in protective cell-mediated immunity against tuberculosis (TB). In the present study, IFN-gamma secretion by peripheral blood mononuclear cells (PBMCs) in response to M. tuberculosis ESAT-6 in Brazilian TB patients was investigated in relation to clinical disease types, such as pleurisy and cavitary pulmonary TB. Leprosy patients, patients with pulmonary diseases other than TB, and healthy donors were assayed as control groups. Sixty percent of the TB patients indeed recognized M. tuberculosis ESAT-6, as did 50% of the leprosy patients and 60% of the non-TB controls. Nevertheless, the levels of IFN-gamma in response to the antigen ESAT, but not to antigen 85B (Ag85B) and purified protein derivative (PPD), were significantly lower in controls than in patients with treated TB or pleural or cavitary TB. Moreover, according to Mycobacterium bovis BCG vaccination status, only 59% of the vaccinated TB patients responded to ESAT in vitro, whereas 100% of them responded to PPD. Both CD4 and CD8 T cells were able to release IFN-gamma in response to ESAT. The present data demonstrate the specificity of ESAT-6 of M. tuberculosis and its ability to discriminate TB patients from controls, including leprosy patients. However, to obtain specificity, it is necessary to include quantitative IFN-gamma production in response to the antigen as well, and this might limit the use of ESAT-6-based immunodiagnosis of M. tuberculosis infection in an area of TB endemicity.     

Enzyme-linked immunospot assay for interferon-gamma in the diagnosis of tuberculous pleurisy

Patients presenting with pleural effusion of undetermined aetiology were prospectively enrolled, and an enzyme-linked immunospot (ELISPOT) assay on pleural fluid and peripheral blood was performed. Forty patients were studied, including 19 with culture- or biopsy-confirmed ( n  = 15) or clinically compatible ( n  = 4) tuberculous pleurisy, and 21 with pleural effusions due to non-tuberculous causes. The sensitivity, specificity and positive and negative predictive values of the assay were 94.7%, 85.7%, 85.7% and 94.7%, respectively, on pleural fluid, and 77.8%, 90.5%, 87.5% and 82.6%, respectively, on blood. Antigen-specific, interferon-gamma-secreting T-cells were concentrated eight to ten times in pleural fluid as compared with blood. Among the seven patients not suitable for pleural biopsy and three patients whose biopsy results were non-diagnostic, nine had positive ELISPOT result with pleural fluid. The ELISPOT assay for interferon-gamma can accurately diagnose tuberculous pleurisy and is helpful for patients not suitable for pleural biopsy and those whose biopsy results are non-diagnostic.     

T-Cell Helper Activity and B-Cell Function of Synovial and Blood Lymphocytes from Patients with Rheumatoid Arthritis or Other Forms of Chronic Arthritis

The helper effect of T cells on B-cell immunoglobulin (Ig) responses induced by pokeweed mitogen (PWM) or purified protein derivative of tuberculin (PPD) was studied in lymphocytes from synovial fluid (SF) and blood of nine patients with rheumatoid arthritis (RA) and eight patients with other forms of chronic arthritis. In PWM cultures the helper effect of SF T cells on Ig responses (IgG, IgM, IgA) of autologous and allogeneic blood B cells was lower than that of blood T cells (P less than 0.01). This decrease was more pronounced in patients with RA than in patients with non-RA. In PPD cultures no significant difference was found between the helper effect of SF T cells and blood T cells on the Ig responses of allogeneic blood B cells or on the IgG response of autologous blood B cells, whereas the helper effect of SF T cells on the IgM and IgA responses of autologous blood B cells was decreased. The Ig responses to PWM or PPD in cocultures of autologous blood B and T cells were not significantly different between patients and healthy controls. The PWM- and PPD-induced Ig responses of SF B cells were lower than those of blood B cells when cocultured with autologous blood T cells. SF B cells produced IgG but usually little IgM and IgA. Thus there was a dysfunction of SF B cells and of SF T cells in a PWM-driven system, but a fairly good helper function of SF T cells in a PPD-driven system.     

Increased Fas and Bcl-2 expression on peripheral blood T and B lymphocytes from juvenile-onset systemic lupus erythematosus, but not from juvenile rheumatoid arthritis and juvenile dermatomyositis

Defective regulation of apoptosis may play a role in the development of autoimmune diseases. Fas and Bcl-2 proteins are involved in the control of apoptosis. The aims of this study were to determine the expression of Fas antigen and Bcl-2 protein on peripheral blood T and B lymphocytes from patients with juvenile-onset systemic lupus erythematosus (JSLE), juvenile rheumatoid arthritis (JRA) and juvenile dermatomyositis (JDM). Thirty-eight patients with JSLE, 19 patients with JRA, 10 patients with JDM and 25 healthy controls entered the study. Freshly isolated peripheral blood mononuclear cells (PBMC) were stained for lymphocyte markers CD3, CD4, CD8, CD19 and for Fas and Bcl-2 molecules. Expressions were measured by three-color flow cytometry. Statistical analysis was performed using Kruskal-Wallis test. Percentages of freshly isolated T lymphocytes positively stained for Fas protein from JSLE patients were significantly increased compared to healthy controls, patients with JRA and patients with JDM. Percentages of B lymphocytes positive for Fas from JSLE patients were higher than healthy controls and JRA patients. In addition, Fas expression on T cells from patients with JRA was increased compared to JDM patients. Otherwise, Fas expression on T and B cells from JRA and JDM patients were similar to healthy controls. MFI of Bcl-2 positive T lymphocytes from JSLE patients were significantly increased compared to healthy controls and JRA patients. MFI of Bcl-2 protein on B lymphocytes from JSLE patients was similar to healthy controls and patients with JRA and JDM. Bcl-2 expression did not differ between JRA and JDM patients and healthy controls. In conclusion, increased expression of Fas and Bcl-2 proteins observed in circulating T and B lymphocytes from patients with JSLE, but not from patients with JRA and JDM, suggests that abnormalities of apoptosis may be related to the pathogenesis of JSLE and probably are not a result of chronic inflammation.     

Cellular immunity in tuberculous pleural effusions: evidence of spontaneous lymphocyte proliferation and antigen-specific accelerated responses to purified protein derivative (PPD).

The kinetics of in vitro cellular proliferation against a PPD of Mycobacterium tuberculosis or streptococcal antigen (streptokinase-streptodornase) was evaluated in pleural fluid and peripheral blood mononuclear cells (PBMC) from patients with tuberculous and non-tuberculous pleuritis. The peak proliferative response to PPD by mononuclear cells from pleural fluid occurred earlier (day 3) in 65% of patients with tuberculosis, a finding not seen in non-tuberculous effusions. Spontaneous lymphocyte proliferation of both peripheral blood lymphocytes and pleural effusion lymphocytes was frequently observed, irrespective of etiology. However, 20 of 21 tuberculous patients manifesting spontaneous lymphocyte proliferation had accelerated kinetics of proliferation to PPD, which was antigen-specific. These results suggest that spontaneous lymphocyte proliferation occurs as a response to antigen stimulation at the site of disease, and is not a non-specific response to inflammation. Furthermore, enhanced reactivity against mycobacterial antigen, manifested by accelerated kinetics of proliferation, has diagnostic potential in patients with pleural effusions.