In Situ Activation of Helper T Cells in the Lung

Raju, Bindu; Tung, Chung F.; Cheng, Debbie M.; Yousefzadeh, Nora; Condos, Rany; Rom, William N.; Tse, David K.

doi:10.1128/iai.69.8.4790-4798.2001

Cited by 31 publications

(27 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1, B and C). Similar to our previous report (40), alveolar macrophages were, on the average, 4 times more prevalent than alveolar lymphocytes in BAL fluid. Therefore, 90% of the total CXCR4 was found on the surface of alveolar macrophages in the mycobacteria-infected lung (Fig.…”

Section: Cxcr4 Expression Is Increased During M Tb Infection In Vivosupporting

confidence: 78%

“…Labeling for flow cytometry was performed as previously described (40). Briefly, BAL cells were reacted with mixtures containing FITC-anti-CD45 and allophycocyanin-anti-CD14, or FITC-anti-CD14, PerCP-anti-CD3, PE-anti-CCR5, and allophycocyanin-anti-CXCR4; treated with FACS lysing solution; washed; fixed; and analyzed on a FACSCalibur (BD Immunocytometry Systems, Mountain View, CA).…”

Section: Flow Cytometrymentioning

confidence: 99%

See 1 more Smart Citation

Mycobacterium tuberculosis-Induced CXCR4 and Chemokine Expression Leads to Preferential X4 HIV-1 Replication in Human Macrophages

Hoshino

Tse²,

Rochford

et al. 2004

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Opportunistic infections such as pulmonary tuberculosis (TB) increase local HIV-1 replication and mutation. As AIDS progresses, alteration of the HIV-1 gp120 V3 sequence is associated with a shift in viral coreceptor use from CCR5 (CD195) to CXCR4 (CD184). To better understand the effect of HIV/TB coinfection, we screened transcripts from bronchoalveolar lavage cells with high density cDNA arrays and found that CXCR4 mRNA is increased in patients with TB. Surprisingly, CXCR4 was predominately expressed on alveolar macrophages (AM). Mycobacterium tuberculosis infection of macrophages in vitro increased CXCR4 surface expression, whereas amelioration of disease reduced CXCR4 expression in vivo. Bronchoalveolar lavage fluid from TB patients had elevated levels of CCL4 (macrophage inflammatory protein-1β), CCL5 (RANTES), and CX3CL1 (fractalkine), but not CXCL12 (stromal-derived factor-1α). We found that M. tuberculosis infection of macrophages in vitro increased viral entry and RT of CXCR4, using HIV-1, but not of CCR5, using HIV-1. Lastly, HIV-1 derived from the lung contains CD14, suggesting that they were produced in AM. Our results demonstrate that TB produces a permissive environment for replication of CXCR4-using virus by increasing CXCR4 expression in AM and for suppression of CCR5-using HIV-1 by increasing CC chemokine expression. These changes explain in part why TB accelerates the course of AIDS. CXCR4 inhibitors are a rational therapeutic approach in HIV/TB coinfection.

show abstract

Section: Cxcr4 Expression Is Increased During M Tb Infection In Vivosupporting

confidence: 78%

Section: Flow Cytometrymentioning

confidence: 99%

Mycobacterium tuberculosis-Induced CXCR4 and Chemokine Expression Leads to Preferential X4 HIV-1 Replication in Human Macrophages

Hoshino

Tse²,

Rochford

et al. 2004

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…CD3 ϩ CD4 ϩ T cells were the dominant lymphocyte subset in the cerebrospinal fluid and they coexpressed CD45RA ϩ and CD45RO ϩ , a phenotype identical with alveolar CD4 ϩ lymphocytes recovered from the lungs of pulmonary tuberculosis patients (23). In healthy individuals, the peripheral blood contains small numbers of these CD45RA ϩ CD45RO ϩ helper T cells that primarily produce IFN-␥ and are in the cell cycle (24,25).…”

Section: Discussionmentioning

confidence: 99%

The Clinical Benefit of Adjunctive Dexamethasone in Tuberculous Meningitis Is Not Associated with Measurable Attenuation of Peripheral or Local Immune Responses

Simmons

Thwaites

Quyen

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

Outcome from tuberculous meningitis (TBM) is believed to be dependent on the severity of the intracerebral inflammatory response. We have recently shown that dexamethasone improved survival in adults with TBM and postulated that the clinical effect would be associated with a measurable systemic and intracerebral impact on immunological markers of inflammation. Prolonged inflammatory responses were detected in all TBM patients irrespective of treatment assignment (placebo or dexamethasone). The inflammatory response in the cerebrospinal fluid was characterized by a leukocytosis (predominantly CD3+CD4+ T lymphocytes, phenotypically distinct from those in the peripheral blood), elevated concentrations of inflammatory and anti-inflammatory cytokines, chemokines, and evidence of prolonged blood-brain barrier dysfunction. Dexamethasone significantly modulated acute cerebrospinal fluid protein concentrations and marginally reduced IFN-γ concentrations; other immunological and routine biochemical indices of inflammation were unaffected. Peripheral blood monocyte and T cell responses to Mycobacterium tuberculosis Ags were also unaffected. Dexamethasone does not appear to improve survival from TBM by attenuating immunological mediators of inflammation in the subarachnoid space or by suppressing peripheral T cell responses to mycobacterial Ags. These findings challenge previously held theories of corticosteroid action in this disease. An understanding of how dexamethasone acts in TBM may suggest novel and more effective treatment strategies.

show abstract

“…Several authors have shown that the pleural fluid of TB patients contain a high number of IFN-γ producer cells (Barnes et al 1993, Robinson et al 1994, Raju et al 2001, and they suggest that these cells may migrate to the lung and pleural tissue during the active disease, and therefore they may be reduced, temporarily, in the peripheral blood. This fact might explain the lower levels of IFN-γ found before the use of anti-TB drugs in this study.…”

Section: Dosage Of Ifn-γ and Other Cytokines -mentioning

confidence: 99%

Pulmonary tuberculosis: evaluation of interferon-gamma levels as an immunological healing marker based on the response to the Bacillus Calmette-Guerin

Moura¹,

Toledo²,

Oliveira

et al. 2004

Mem. Inst. Oswaldo Cruz

View full text Add to dashboard Cite

Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis whose interaction with the host may lead to a cell-mediated protective immune response. The presence of interferon-γ (IFN-γ) is related to this response. With the purpose of understanding the immunological mechanisms involved in this protection, the lymphoproliferative response, IFN-γ and other cytokines like interleukin , and tumor necrosis factor alpha (TNF-α) Key words: tuberculosis -interleukin-5 -interleukin-10 -tumor necrosis factor alpha -interferon-γ -peripheral blood mononuclear cells Tuberculosis (TB), a chronic infective-contagious disease, is caused by Mycobacterium tuberculosis and remains an important public health problem whose mechanisms related to a protective immunity in humans are not clear. The resurgence of TB has stimulated studies for the development of vaccines, new diagnostic methods and less toxic and more effective drugs for treatment (Laal et al. 1997). The cellular immunity plays an important role in TB healing (Ladel et al. 1997, Torres et al. 1998, Turner et al. 2000, Chackerian et al. 2001). Resistance to mycobacterial infections is conferred by immunological mechanisms mediated by T CD4 + lymphocytes, involving cytokines that increase the microbicide activity of macrophages (Dlugovitzky et al. 2000, Oberholzer et al. 2000. Studies in murine and human models allow differentiating two subpopulations of T CD4 + lymphocytes termed Th1 and Th2, that mediate the protection or the aggravation of the disease (Ladel et al. 1997, Kori et al. 2000. This existing dichotomy between the protective or non-protective immune responses is likely to be correlated with cytokine patterns produced by different subpopulations of lymphocytes during initial surviving stages of the pathogens inside macrophages. Interferon-γ (IFN- γ) acts as a powerful macrophage activator, increasing the molecule expression of the main class II histocompatibility complex and the potentialization of the cell response, including the production of cytokines, nitric oxide, and the increase of the cytolitic activity, with a main role in the Th1 type (Flesh et al. 1995). Studies carried out by Cooper et al. (1993) and Flynn et al. (1993) demonstrated that mice without the IFN-γ gene were not able to fight off the infection caused by M. tuberculosis. In humans, individuals who presented genetic mutations in the receptors for IFN-γ were observed to have had a high susceptibility to acquire infections caused by atypical mycobacteria (Jouanguy et al. 1996), suggesting an important role of IFN-γ in the protective response against TB.Besides the importance of better understanding the immunological mechanisms that may contribute to the healing, it becomes essential to determine markers of healing lesions, once this is currently carried out based on the clinical, radiological, and negative bacterioscopy.In this work, we proposed the in vitro evaluation of IFN-γ levels produced by peripheral blood mononuclear cells (PBMC) after Bacillus Calmette-Guerin (BCG) stimulati...

show abstract

In Situ Activation of Helper T Cells in the Lung

Cited by 31 publications

References 49 publications

Mycobacterium tuberculosis-Induced CXCR4 and Chemokine Expression Leads to Preferential X4 HIV-1 Replication in Human Macrophages

Mycobacterium tuberculosis-Induced CXCR4 and Chemokine Expression Leads to Preferential X4 HIV-1 Replication in Human Macrophages

The Clinical Benefit of Adjunctive Dexamethasone in Tuberculous Meningitis Is Not Associated with Measurable Attenuation of Peripheral or Local Immune Responses

Pulmonary tuberculosis: evaluation of interferon-gamma levels as an immunological healing marker based on the response to the Bacillus Calmette-Guerin

Contact Info

Product

Resources

About