PubMed Health⌕ Search

Biomedical subjects

Homer L Twigg

Publications and source records attributed to Homer L Twigg.

13 recordsLinked to original sources
PubMed2006

Functional impairment of CD4 T cells despite normalization of T cell number in HIV.

Using an in vitro model, we demonstrate that when CD4 T cells from HIV infected subjects are enriched from total blood lymphocytes the immune response to antigen is augmented. However, augmentation of this response is confined to HIV infected subjects with relatively preserved CD4 T cell counts. Enriching for CD4 T cells had no effect on antigen responses in patients with low CD4 lymphocyte counts. These findings support the concept that CD4 T cells in late stage HIV have inherent qualitative defects.

Adult↗
PubMed2006

Cytometric analysis of BAL T cells labeled with a standardized antibody cocktail correlates with immunohistochemical staining.

BACKGROUND: Determining T-cell phenotypes of lung cells obtained by bronchoalveolar lavage (BAL) is frequently clinically useful, particularly for evaluating causes of interstitial lung disease. The current standard of determining CD4/CD8 T-cell subsets by immunohistochemical (IHC) staining of cytocentrifuge slides is labor-intensive and subject to interpreter variation. Flow cytometry (FCM) is a precise and rapid method commonly used in research to characterize cells in the lung. However, few studies address the methodology of analysis of BAL lymphocytes by FCM. METHODS: Patients underwent bronchoscopy for clinical purposes. A BAL cell differential and T-cell subtype was requested by the treating physician to supplement the evaluation of patients with suspected interstitial lung disease. We used a commercially available T-cell antibody reagent, approved for analysis of blood via FCM, for T-cell subtyping of clinical BAL specimens. RESULTS: The percentages of CD4 and CD8 T-cell populations, as well as the CD4/CD8 ratios showed excellent correlation with IHC staining of cytocentrifuge slides regardless of the acquisition program used, as long as the gating strategy remained consistent (r > or = 0.9693 for CD4, r > or = 0.9589 for CD8, and r > or = 0.9485 for the CD4/CD8 ratio). CONCLUSION: These findings validate the use of standardized, commercially available antibody cocktails for BAL lymphocyte subtyping, making this technique available to clinicians and researchers with access to a three-color or four-color flow cytometer.

Antibodies↗
PubMed2005

Apoptosis of CD57+ and CD57- lymphocytes in the lung and blood of HIV-infected subjects.

Patients infected with HIV frequently have a CD8+ lymphocytic alveolitis consisting of HIV-specific CD8+CD57- cytotoxic T lymphocytes. However, in late stage disease, there is expansion of a CD8+CD57+ population with suppressive properties. We examined role of lymphocyte apoptosis in the expansion of the CD8+CD57+ lymphocytes in late stage HIV in the lung and blood compartment in human subjects. Fas was expressed on virtually all lung lymphocytes from HIV-infected and normal subjects. Fas ligand expression was increased in HIV infection in both CD8+CD57+ and CD8+CD57- lymphocytes, though a significantly greater percentage of CD8+CD57+ cells expressed this marker. CD8+CD57+ lymphocytes in normal and HIV-infected subjects underwent more apoptosis than CD8+CD57- cells. However, in late stage HIV infection, the percentage of CD8+CD57+ cells undergoing apoptosis declined. These data demonstrate that under normal conditions CD8+CD57+ cells appear destined to undergo programmed cell death. Expansion of suppressive CD8+CD57+ cells in the lungs of HIV-infected subjects with advanced disease may be due to the failure of this normal regulatory process.

Apoptosis↗
PubMed2005

Outcomes of American Lung Association-Indiana Lung Centers asthma program.

The American Lung Association of Indiana (ALA-I), in conjunction with participating Indiana hospitals, developed the Lung Center concept as a mechanism to provide standardized delivery of lung health education. The goal of this pilot study was to evaluate initial experience with the Lung Center program "Overcoming Your Asthma," a two-session asthma education program, and identify areas needing improvement. A total of 305 participants responded to a 31-item questionnaire at baseline (immediately prior to program exposure) and again at 1 month (n = 75) and 6 months (n = 30) after participation. Overall, delivery of the ALA-I Lung Center asthma education program improved respondents' experience with asthma. At one month after the educational session, the program improved participant knowledge about asthma. This was associated with modest improvements in treatment behaviors, economic outcomes and asthma symptoms such as reduced breathing difficulties, wheezing and asthma exacerbations, and improvement in sleep. Improvements were not uniformly sustained at 6 months. In summary, the Lung Center asthma education program appears to benefit patients with asthma. The results provide preliminary evidence to support continued delivery of asthma education in Lung Centers. Future efforts should emphasize education to improve treatment attitudes and behaviors.

Asthma↗
PubMed2005

Humoral immune defense (antibodies): recent advances.

The humoral, or antibody, immune response is essential for host defense against bacterial pathogens. The lung has the ability to respond quickly to some pathogens through stimulation of resident antigen-specific memory B cells. Alternatively, after exposure to a new pathogen, the lung can generate de novo both a systemic and local (mucosal) antibody response. The resulting production of antigen-specific IgG and IgA act in concert to help clear the invading pathogen and reduce subsequent colonization of respiratory epithelium. Systemic vaccination against respiratory pathogens, although effective in generating systemic IgG responses and some mucosal IgA responses, may be less effective than vaccination through mucosal surfaces, which induce a brisk IgA and IgG response both locally and systemically depending on the site of antigen deposition. The local response is important in reducing colonization of the upper respiratory tract by pathogenic bacteria, the first step in the development of most causes of pneumonia. Future studies are needed to provide further insight on the site of pulmonary humoral host responses to bacterial challenge and optimal vaccine regimens to minimize the burden of respiratory disease caused by pathogenic bacteria.

Antibodies, Bacterial↗
PubMed2004

Human immunodeficiency virus gp120 downregulates CD1d cell surface expression.

CD1d is an MHC class I-like surface molecule that presents endogenous glycoplipid antigens. The effect of HIV infection on CD1d surface expression has not yet been reported. FACS analysis revealed significantly lower levels of CD1d on CD14(+) monocytes from HIV-infected subjects compared to HIV-infected subjects on HAART and healthy controls. CD1d expression correlated inversely with viral load in infected individuals. CD1d surface expression on human cell lines was downregulated after infection with M-tropic HIV, T-tropic HIV, or after exposure to HIV gp120 in vitro. These data suggest that CD1d-mediated responses are altered during HIV infection and may thus contribute to the global immunodeficiency seen in these patients.

Antigens, CD1↗
PubMed2004

Macrophages exposed to lymphotropic and monocytotropic HIV induce similar CTL responses despite differences in productive infection.

Macrophages are accessory cells that are vulnerable to infection by HIV-1. HTLV-IIIB, a lymphotropic strain of HIV, infects macrophages poorly resulting in either no or low levels of virus expression compared to high levels of productive infection after exposure of macrophages to the monocytotropic HIV strain Ada-M. Whether this results in an impaired ability of HTLV-IIIB-exposed macrophages to initiate protective cytotoxic T lymphocyte (CTL) immune responses against these strains is not well defined. We investigated the ability of monocyte-derived macrophages (MDM) exposed to lymphotropic and monocytotropic HIV strains to initiate primary CTL responses in vitro. MDM exposed to HTLV-IIIB induced a specific primary CTL response that was comparable to MDM exposed to the monocytotropic strain Ada-M despite marked differences in productive HIV infection in MDM between the two strains. CTL generated in this model were MHC-restricted, strain-specific, and CD8+. These data demonstrate that high levels of productive HIV infection in accessory cells are not a prerequisite for the generation of a primary CTL response, suggesting a novel immunologic interaction between MDM and lymphotropic HIV strains.

CD4-Positive T-Lymphocytes↗
PubMed2004

Macrophages in innate and acquired immunity.

Alveolar macrophages play a central role in pulmonary host defense. When foreign particles or pathogens enter the respiratory tract, constitutively present innate host defenses attempt to clear the challenge. Alveolar macrophage phagocytosis of foreign material is a critical component of this response, as is secretion of inflammatory mediators designed to combat invading pathogens. If the pathogenic burden is too large and overwhelms innate immunity, then acquired immune responses are initiated resulting in the generation of antigen-specific cellular and humoral immunity. In response to evolutionary pressures to minimize unnecessary inflammation in the lower respiratory tract, alveolar macrophages are generally poor accessory cells in the initiation of specific immunity. However, in many circumstances, especially those associated with cellular activation, alveolar macrophages can play an important role in the generation and expansion of pulmonary immune responses. This review discusses the role of alveolar macrophages in innate and acquired pulmonary host defense.

Journal Article↗
PubMed2003

Alveolar macrophages from HIV-infected subjects are resistant to Mycobacterium tuberculosis in vitro.

HIV-infected individuals frequently develop Mycobacterium tuberculosis (MTB) infection. Alveolar macrophages (AM) are the initial host defense against this organism. We measured MTB growth in AM from normal and HIV-infected subjects after in vitro exposure. Intracellular growth of MTB was reduced in AM from HIV-infected subjects compared with normal macrophages. This was confined to subjects with CD4 counts greater than 200/microl. Growth of avirulent mycobacteria in HIV macrophages was significantly less than virulent MTB. Because avirulent MTB is more sensitive to tumor necrosis factor-alpha (TNF-alpha), we examined the relationship between cytokine secretion and mycobacterial growth. Higher AM spontaneous TNF-alpha secretion was associated with reduced MTB growth in normal AM. This relationship was not seen in HIV-infected subjects, suggesting that other factors contributed to mycobacteria resistance. Mycobacteria-induced TNF-alpha secretion was inversely associated with growth in normal AM but not in HIV-infected subjects. Finally, binding and internalization of MTB was augmented in HIV macrophages compared with normal, demonstrating that reduced intracellular MTB growth was not due to impaired phagocytosis. In conclusion, the increased incidence of MTB infection in HIV-infected subjects does not appear to be due to a defect in macrophage innate immunity.

Adult↗
PubMed2003

Pulmonary immunoglobulin responses to Streptococcus pneumoniae are altered but not reduced in human immunodeficiency virus-infected Malawian adults.

We tested the hypothesis that human immunodeficiency virus (HIV)-infected adults have a specific defect in anti-pneumococcal capsular polysaccharide (Pn-specific) immunoglobulin (Ig) in fluid obtained from the lower respiratory tract. Higher levels of total IgG and IgM were present in bronchoalveolar lavage samples from HIV-infected subjects than in those from HIV-uninfected subjects. Pn-specific IgG and IgM in bronchoalveolar lavage samples were not significantly different between HIV-infected and -uninfected subjects. After pneumococcal infection, HIV-infected patients had higher bronchoalveolar lavage levels of Pn-specific IgG than HIV-infected patients without recent infection (geometric means, 387 vs. 30 ng/mL, P=.001).

AIDS-Related Opportunistic Infections↗
PubMed2003

Histoplasmosis after treatment with anti-tumor necrosis factor-alpha therapy.

Anti-tumor necrosis factor-alpha (TNF-alpha) antibodies are frequently used to treat inflammatory diseases. However, these drugs also have immunosuppressive effects. We report on three patients who developed disseminated histoplasmosis on therapy with TNF-alpha inhibitors. In vitro assays were used to characterize the role of these agents in host defense against Histoplasma capsulatum. Intracellular proliferation of H. capsulatum was measured in alveolar macrophages and peripheral monocytes of normal volunteers in the presence and absence of the TNF-alpha antibody, infliximab. Both infliximab and control antibody enhanced fungal growth in monocytes and alveolar macrophages, suggesting this was a nonspecific antibody response. Despite similar intracellular fungal loads in the presence of both antibodies, lymphocyte proliferation in response to blood monocytes and alveolar macrophages infected with H. capsulatum was inhibited by the addition of physiologic doses of infliximab, whereas control antibody had no effect. The production of H. capsulatum-induced interferon-gamma and TNF-alpha was assessed in 5-day cultures containing lymphocytes and alveolar macrophages or monocytes. Interferon-gamma secretion was significantly reduced in the presence of infliximab. In summary, patients receiving anti-TNF-alpha therapy are at risk for developing disseminated histoplasmosis. This may be due to a defect in the TH1 arm of cellular immunity.

Adolescent↗
PubMed2003

Measurements of HIV viral loads from different levels of the respiratory tract.

BACKGROUND: The lung is a common site of disease in HIV infection. Virus has been detected in BAL fluid (BALF) and saliva. However, the relationship between viral loads detected at different levels of the respiratory tract is unknown. METHOD: We measured simultaneous HIV viral loads in parotid saliva (PS), bronchial fluid (BF), BALF, and plasma by reverse transcription polymerase chain reaction in 20 HIV-infected individuals. RESULTS: HIV was detected in 53% of BALF samples, 15% of BF samples, 5% of PS samples, and 88% of plasma samples. Viral loads in plasma and BALF samples were positively correlated. There were significantly higher levels of HIV viral load in both plasma and BALF in subjects with CD4 counts of < 200 cells/ microL compared to those with higher counts. Antiretroviral therapy (ART) was associated with lower BALF and plasma viral loads, and the effect in BALF was independent of the plasma viral load. Interestingly, smoking also was associated with lower levels of both BAL and BF viral loads, independent of the plasma viral load. CONCLUSION: These data demonstrate that while HIV can be detected in the respiratory tract, the viral load is influenced by both local factors (ie, level of the respiratory tree and cigarette smoking) and systemic factors (ie, ART and peripheral CD4 count).

Adult↗