Susceptibility to pulmonary disease due to Mycobacterium avium–intracellulare complex may reflect low IL-17 and high IL-10 responses rather than Th1 deficiency

It remains unclear why some individuals and not others are susceptible to non-tuberculous mycobacterial lung disease (NTMLD). To determine whether NTMLD is associated with defects or biases in Th1/Th2/Th17 immunity, blood leukocytes from NTM patients with nodular bronchiectasis, their adult offspring, and healthy population controls were stimulated with staphylococcal enterotoxin B (SEB), tuberculin and sensitin to measure cytokine production. In response to SEB, NTM patients exhibited higher frequencies of IFNγ-producing CD4⁺ T cells than population controls (P < 0.001). In supernatant, levels of IL-17 were lower in patients than adult offspring. Sensitin elicited higher IFNγ responses from patients than controls (P < 0.05). Patients also produced more IL-10 in supernatant than controls after culture with tuberculin (P < 0.01) or sensitin (P < 0.05), but IL-10-producing CD4⁺ T cells were undetectable. NTMLD is not associated with deficient IFNγ production, but may be associated with reduced Th17 immunity and/or a predisposition towards IL-10 production from non-CD4⁺ T cells.     

Autoreactive T-cell responses in primary biliary cirrhosis are proinflammatory whereas those of controls are regulatory

BACKGROUND & AIMS: Autoreactive T cells that proliferate in response to autoantigens are found in both autoimmune disease and controls but have important qualitative differences in relative activation states, costimulation signal requirements, and pathogenetic significance. Understanding the mechanism for activation of autoreactive T cells will be critical in the treatment of autoimmune diseases. METHODS: To understand the differences between autoreactive T cells in primary biliary cirrhosis (PBC) versus controls, we have developed autoreactive T-cell clones (TCCs) from patients with PBC and healthy controls and have used a peptide corresponding to the CD4 major autoepitope to define the relative proliferative and cytokine response. RESULTS: Using an enzyme-linked immunosorbent spot assay, peripheral blood mononuclear cells (PBMCs) from PBC, but not from controls, produce interferon (IFN)-gamma regardless of whether costimulation-competent or -incompetent antigen-presenting cells (APC) were used. In contrast, a significant number of IFN-gamma-producing cells were found in PBMCs from controls but only if costimulation-competent PBMCs presented an autoantigenic peptide. In addition, costimulation-dependent autoreactive TCCs became anergic after a single round of stimulation in the presence of APC that did not provide a costimulatory signal, whereas some costimulation-independent autoreactive TCCs required repeated stimulation to become anergic and the others did not become anergic. Finally, anergic TCCs produced interleukin-10, but no IFN-gamma, and exhibited regulatory functions in an antigen-dependent, cell contact-independent, and partially interleukin-10-mediated manner. CONCLUSIONS: These data relate specifically to the functional characteristics of autoreactive T cells in PBC but are also generically important for understanding the mechanisms for generating pathogenetic autoreactive T cells.     

Complications of presumed ocular tuberculosis

Acta Ophthalmol. 2010: 88: 905–909

Abstract.

Purpose: To determine the effect of steroid treatment on visual outcome and ocular complications in patients with presumed ocular tuberculosis. Methods: Retrospective review of patients with presumptive ocular tuberculosis. The clinical diagnosis was made based on ocular findings, positive purified protein derivative (PPD) testing of more than 15 mm induration, exclusion of other causes of uveitis and positive ocular response to anti‐tuberculous therapy (ATT) within 4 weeks. Group 1 included patients who had received oral prednisone or subtenon injection of triamcinolone acetonide prior to ATT. Group 2 included patients who did not receive corticosteroid therapy prior to administration of ATT. Results: Among 500 consecutive new cases of uveitis encountered in 1997–2007 there were 49 (10%) patients with presumed ocular tuberculosis. These comprised 28 (57%) male and 21 (43%) female patients with a mean age of 45 years (range 12–76 years). Four (20%) patients in group 1 had initial visual acuity of 20/40 or better, in comparison to eight (28%) patients in group 2. At 1‐year follow‐up, six (30%) patients in group 1 had a visual acuity of 20/40 or better compared with 20 (69%) patients in group 2 (p = 0.007). Of 20 eyes (26%) in group 1 that had visual acuity of < 20/50 at 1‐year follow up, 14 (70%) eyes developed severe chorioretinal lesion (p = 0.019). Conclusion: Early administration of corticosteroids without anti‐tuberculous therapy in presumed ocular tuberculosis may lead to poor visual outcome compared with patients who did not receive corticosteroids prior to presentation. Furthermore, the severity of chorioretinitis lesion in the group of patients given corticosteroid prior to ATT may account for the poor visual outcome.     

曲阜市中小学生结核分枝杆菌感染状况调查

目的了解曲阜市城乡中小学生结核分枝杆菌的感染状况,为结核病防治提供可靠的科学依据.方法对曲阜市部分城乡4 437名中小学生进行结核菌素(PPD)试验,并对PPD强阳性者进行透视、拍片、血沉、痰结核菌等检查.结果调查4 437名学生,PPD阳性者539例,感染率为12.15%.结论中小学生的结核分枝杆菌感染不容忽视,将结核病筛查纳入学校的制度化管理非常必要.     

PPD皮肤试验在结核病临床诊断中的应用

目的研究纯结核蛋白衍生物(PPD)皮肤试验阳性反应强度在肺结核病的鉴别诊断及传染性判断中的应用价值。方法对福建省龙岩市结核病防治所1998~2003年门诊确诊的活动性肺结核315例(其中涂阳172例,涂阴143例),非结核性呼吸道疾病患者137例,常规进行PPD皮肤试验,观察结核与非结核呼吸道疾病患者、涂阳肺结核与涂阴肺结核之间PPD反应强度,应用χ2检验进行比较。结果(1)结核病人与非结核病人PPD反应阳性率比较有显著性差异。(2)涂阳肺结核病人与涂阴肺结核病人PPD反应阳性率比较无显著性差异。结论(1)PPD试验有助于鉴别临床疑似肺结核病。(2)PPD阳性率与肺结核的传染性无关。     

HIV感染者CD4细胞计数与结核菌素试验结果分析

目的了解HIV感染者CD4细胞计数、结核菌素（PPD）反应及两者的相互影响情况。方法抽取2032例HIV感染者进行CD4细胞计数和5U的PPD试验。结果CD4细胞计数随患者年龄的增加而明显下降，CD4计数小于等于200个/mm^3者占25％，大于等于500个/mm^3者21．4％，位于两者之间者53．6％；PPD反应阳性率14．7％，随年龄的增加而呈上升趋势；CD4细胞计数与PPD反应呈负相关，但无统计学意义（P〉0．05）。结诊HIV感染者中PPD反应阳性率较低；PPD反应与CD4细胞计数呈负相关但无统计学意义（P＞0.05）。     

Clonal distribution of human T cells recognizing PPD in the context of each of two distinct Ia molecules

Participation of two of three distinct human Ia molecules, HLA-DR and the Ia molecule detected by monoclonal antibody (MoAb) 1B4 (1B4 molecules), in antigen presentation for T cell responses to purified protein derivative (PPD) and herpes simplex virus (HSV) was first suggested from studies on the inhibition of proliferative responses of whole T cell populations with MoAb against human Ia molecules. To determine whether a single T cell recognizes the antigen in the context of both Ia molecules or in the context of each one of two Ia molecules, we isolated and propagated PPD-reactive T cell clones from an HLA-DR heterozygous individual. The clones showed four different restriction patterns: type I and type II clones appeared to be restricted to one of two HLA-DR antigens, type III clones gave anomalous patterns of response and seemed to be restricted to non-DR antigens, and type IV clone recognized antigen when both DR antigens were presented on the same APC surface. Blocking study with MoAb to Ia molecules suggested that type I and type II clones are restricted to DR molecules and type III clones are restricted to 1B4 molecules distinct from DR or MB1 molecules. Furthermore, it is most likely that type IV clone was restricted to the interaction molecule associated with DR antigens. These data imply that human T cell clones recognizing PPD in the context of each one of two Ia molecules are clonally distinct.     

Subcultured human endothelial cells can function independently as fully competent antigen-presenting cells

Recent evidence has suggested that dendritic cells, epidermal Langerhan's cells and endothelial cells (EC) as well as macrophages, fulfill the requirements of antigen-presenting cells. Despite a variety of controls, one weakness in the evidence that these latter cell types can independently serve as antigen-presenting cells is that the cell preparations may contain small numbers of contaminating macrophages or other cell types. The experiments described in this paper are directed towards providing firm evidence that human EC are independently capable of presenting antigen to T cells. EC were isolated from human umbilical veins and maintained continuously by serial subculture for periods of up to 8 months. The subcultured EC displayed classic EC morphology and uniform immunofluorescent staining for Factor VIII-related antigen. The subcultured EC (tested to the 18th subculture) presented both particulate and soluble antigens to macrophage-depleted T cells with an efficiency equivalent to freshly isolated cells. Monoclonal antibodies to HLA-DR and HLA-DS determinants inhibited antigen presentation by either autologous macrophages or EC. In addition, antigen presentation by the subcultured EC was not affected by the macrophage-specific monoclonal antibody Mac-120, which inhibited antigen presentation by autologous macrophages in the same experiments. These results are consistent with human EC being able to independently function as fully competent antigen-presenting cells.     

The rubro-olivary tract in the cat, as demonstrated with the method of retrograde transport of horseradish peroxidase

The rubro-olivary projection in the cat was investigated by means of the retrograde transport of horseradish peroxidase. After injections in the inferior olive, more than a thousand labelled neurons were found in the ipsilateral red nucleus. These neurons had triangular-shaped cell bodies with an average diameter of 26.4 +/- 7.7 microns (mean +/- S.E.M.) and had few dendrites. Between 85% and 95% of the rubro-olivary neurons were found in the rostral third of the red nucleus (between A 5.5 and A 7). Morphologically, the rubro-olivary neurons are similar to rubro-thalamic neurons. Previous studies with retrograde transport of horseradish peroxidase have failed to demonstrate an extensive projection from the red nucleus to the inferior olive. These results are discussed in relation to our own findings.