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Background: Lymph node tuberculosis (LNTB) is the most frequent extrapulmonary form of tuberculosis (TB). Studies of human tuberculosis at sites of disease are limited. LNTB provides a unique opportunity to compare local in situ and peripheral blood immune response in active Mycobacterium tuberculosis (Mtb) disease. The present study analysed T regulatory cells (Treg) frequency and activation along with CD4+ T cell function in lymph nodes from LNTB patients., Results: Lymph node mononuclear cells (LNMC) were compared to autologous peripheral blood mononuclear cells (PBMC). LNMC were enriched for CD4+ T cells with a late differentiated effector memory phenotype. No differences were noted in the frequency and mutifunctional profile of memory CD4+ T cells specific for Mtb. The proportion of activated CD4+ and Tregs in LNMC was increased compared to PBMC. The correlation between Tregs and activated CD4+ T cells was stronger in LNMC than PBMC. Tregs in LNMC showed a strong positive correlation with Th1 cytokine production (IL2, IFNγ and TNFα) as well as MIP-1α after Mtb antigen stimulation. A subset of Tregs in LNMC co-expressed HLA-DR and CD38, markers of activation., Conclusion: Further research will determine the functional relationship between Treg and activated CD4+ T cells at lymph node sites of Mtb infection.

Background: Patients suspected of having cervical tuberculous lymphadenitis are diagnosed using investigations such as fine needle aspiration cytology and the polymerase chain reaction for Mycobacterium tuberculosis. However, these investigations are intended for primary tuberculosis infection. The majority of cervical tuberculous lymphadenitis cases in the elderly are thought to be caused by reactivation., Objective: The aims of this study were (1) to examine the efficacy of fine needle aspiration cytology, polymerase chain reaction and blood tests in the diagnosis of cervical tuberculous lymphadenitis caused by reactivation, and (2) to clarify any differences when compared with primarily infected cervical tuberculous lymphadenitis cases., Materials and Methods: Thirty-three elderly patients with neck lumps underwent excisional biopsy from 2003 to 2008. The efficacy of fine needle aspiration cytology was examined by comparing the results of excisional biopsy with those of fine needle aspiration cytology performed at the initial medical examination for cases of suspected tuberculous disease. Furthermore, the leucocyte count and C-reactive protein concentration were compared for cases of cervical tuberculous lymphadenitis versus cases of malignant lymphoma., Results: Although nine cases were diagnosed with cervical tuberculous lymphadenitis using excisional biopsy, only one of these had been suspected based on fine needle aspiration cytology results. Three cases with tuberculous lymphadenitis were suspected of having malignant lymphoma on initial examination. There was no significant difference in the leucocyte count and C-reactive protein concentration, comparing cases of tuberculous lymphadenitis versus malignant lymphoma., Conclusion: Unlike the primary infection often seen in endemic areas, the diagnosis of early stage tuberculous lymphadenitis of the swelling type caused by reactivation in elderly people is difficult to confirm unless excisional biopsy is performed. In elderly patients with neck lumps, cervical tuberculous lymphadenitis should be included in the differential diagnosis.

Background: The immune response to Mycobacterium tuberculosis is complex and multifactorial, the cytokine system being a major factor in M. tuberculosis immunity., Aim: To analyze the immunohistochemical aspects of tuberculous lymph nodes in immunocompetent patients and search for associations between SOCS and cytokine expression in human tuberculous lymphadenitis., Methods: Thirteen lymph nodes were assayed by immunohistochemistry for SOCS-1 and 3, STAT-3, RANTES, MIP-1-alpha, ICAM-1, IFN-gamma as well as CD45RO, CD20, CD34, CD68, trypsin and lysozyme. Additionally, the RT in situ PCR was performed for SOCS-1 and 3 mRNA detection., Results: Decreased MIP-1 alpha expression together with reduced SOCS-3 (p=0.042), lysozyme (p=0.024) and CD45RO (p=0.05) was observed in the TB lymph nodes compared to the control lymph nodes. In conclusion, the lymphadenitis due to M. tuberculosis was associated with a downregulation of memory T cells (CD45RO), activated lysozymes and SOCS-3 compared to controls, which may play a role in the long-term bacterial replication and altered immune modulation characteristic of the disease.

Lymph nodes can be the primary target of infection or malignant transformation and may exhibit characteristic patterns of leukocyte infiltration analogous to those seen in inflammation of other tissues. Leukocyte migration to lymph nodes in vivo is a highly regulated, multi-step process that depends upon adhesion molecules and as yet, uncharacterized chemotactic signals. Chemokines are a key part of the orchestrated code of signals that directs leukocyte subsets to sites of inflammation or immune response. The potential role of these chemoattractants in selective trafficking of leukocyte subsets into lymph nodes was assessed by determining the expression of chemokines on a range of pathological and normal human lymph nodes and by evaluating the cellular composition of each lymph node. In situ hybridization using chemokine riboprobes and immunohistochemistry using specific antibodies were performed in order to correlate the mRNA and protein expression of the chemokines. The cellular source(s) of each chemokine was assessed by immunohistochemical staining of adjacent sections using antibodies directed against distinctive cellular markers. Substantial, but varied, expression of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, RANTES, macrophage chemotactic protein (MCP)-1, eotaxin, and interleukin 8 (IL-8) were detected in the pathological lymph nodes by diverse cell types. Control lymph nodes showed expression only of RANTES, mainly by high endothelial venules. In all lymph nodes, except the nodes infiltrated with breast cancer, chemokine mRNA expression was highly concordant with the corresponding protein. In contrast with in vitro studies that have suggested discrete target cell specificity of chemokines, this study showed that with the possible exception of the neutrophil chemoattractant, IL-8, no chemokine appeared to be uniquely associated with the accumulation of a specific leukocyte subset. These data implicate chemokines in the recruitment of leukocytes to lymph nodes affected by diverse disease states., (Copyright 1999 Academic Press.)

Cells of MPS and lymphatic system in lymph nodes from eighteen patients with culture proven tuberculous lymphadenitis were examined by histological and immunohistochemical technics. Ten patients suffered from symptomatic HIV-infection and eight patients were immunocompetent individuals without HIV serology. Characteristic granulomas with or without caseation were observed in the eight immunocompetent and the four HIV-infected patients with less marked lymphopenia of CD4 positive peripheral blood lymphocytes. In lymph nodes from the other HIV-infected patients with more severe depression of CD4 positive peripheral blood lymphocyte count no epitheloid cell formation was present. Instead of these cells foamy macrophages were found. The phenotype of macrophages underwent progressive changes parallel to decreasing numbers of CD4 positive peripheral blood lymphocytes. Foamy macrophages in mycobacterium avium-intracellulare infection may represent an end-stage phenotype. While many macrophages and lymphocytes expressed IL-2 receptors in cases with typical granulomas there was no such CD25 expression in cases without any epitheloid cell formation. Our results suggest that T-cell activation is necessary for epitheloid granuloma formation in human tuberculosis and preliminary in situ data support the assumption that in vivo the HIV-infection provokes an excess production of cytokines which in turn causes an exhaustion of the immune system and finally AIDS.

Cell suspensions obtained from 54 human lymph nodes involved by different pathological conditions were characterized by conventional markers and by the OKT-3, OKT-4, OKT-8, OKIa-1, and OKM-1 monoclonal antibodies. In 18 cases of reactive lymphoid hyperplasia, the majority of lymph node cells were mature T lymphocytes (E-RFC = 56 +/- 9%; OKT-3+ = 63 +/- 10%); among T-cell subsets, OKT-4+ cells were 49 +/- 8% whereas OKT-8+ cells were 21 +/- 8% (T4/T8 = 2.7 +/- 1.1). This distribution of T-cell phenotypes was not similar in the different histological types of reactive lymphoid hyperplasia. In fact, an increase in the percentage of OKT-8+ cells (25 +/- 9%; P less than 0.05) and a decrease in the values of the T4/T8 ratio (2.1 +/- 1.0; P less than 0.05) were observed in 9 cases of reactive lymphoid hyperplasia of follicular type when they were compared to the mixed and sinus types. In 13 lymph nodes involved by B-cell lymphoma, the percentage of T lymphocytes was markedly reduced (E-RFC = 21 +/- 12%; OKT-3+ = 27 +/- 18%) and the percentage of OKIa-1+ cells (51 +/- 15%) was significantly (P less than 0.01) increased as compared to reactive nodes; in addition, in these cell suspensions, an increase in the relative proportion of OKT-8+ cells (T4/T8 = 1.4 +/- 0.7; P less than 0.01) could also be demonstrated. Finally, a clear prevalence of OKT-4+ cells on OKT-8+ cells was demonstrated in 5 cases of tuberculous lymphadenitis (T4/T8 = 3.9 +/- 1.5; NS) and in 18 cases of Hodgkin's disease (T4/T8 = 4.2 +/- 2.0; P less than 0.01). In tuberculous lymphadenitis, a significant increase (P less than 0.01) in the percentage of OKM-1+ cells could also be demonstrated.

Monoclonal antibodies and immunoperoxidase staining were used to characterize the cellular subpopulations in lymph nodes from 10 patients with tuberculous lymphadenitis, seven of whom had symptomatic human immunodeficiency virus (HIV) infection. CD4+ cells were significantly fewer in nodes of patients with HIV infection than in those of immunocompetent patients. CD8+ cells were distributed throughout the granuloma in patients with HIV infection, but confined to the periphery in normal hosts. Blastoid Ta1+ cells, putatively antigen-reactive T lymphocytes, were seen in immunocompetent patients but not in those with HIV infection, suggesting that these cells fail to mature appropriately in the latter group. The immunopathological features noted above provide preliminary evidence that the cell-mediated immune response to tuberculosis is abnormal in patients with HIV infection, and may in part explain both the severe and the unusual manifestations of tuberculosis in these individuals.