Bronchoalveolar CD4+ T cell responses to respiratory antigens are impaired in HIV-infected adults

Abstract

RationaleHIV-infected adults are at an increased risk of lower respiratory tract infections. HIV infection impairs systemic acquired immunity, but there is limited information in humans on HIV-related cell-mediated immune defects in the lung.ObjectiveTo investigate antigen-specific CD4+ T cell responses to influenza virus, Streptococcus pneumoniae and Mycobacterium tuberculosis antigens in bronchoalveolar lavage (BAL) and peripheral blood between HIV-infected individuals and HIV-uninfected Malawian adults.MethodsWe obtained BAL fluid and blood from HIV-infected individuals (n=21) and HIV-uninfected adults (n=24). We determined the proportion of T cell subsets including naive, memory and regulatory T cells using flow cytometry, and used intracellular cytokine staining to identify CD4+ T cells recognising influenza virus-, S pneumoniae- and M tuberculosis-antigens.Main resultsCD4+ T cells in BAL were predominantly of effector memory phenotype compared to blood, irrespective of HIV status (p<0.001). There was immune compartmentalisation with a higher frequency of antigen-specific CD4+ T cells against influenza virus, S pneumoniae and M tuberculosis retained in BAL compared to blood in HIV-uninfected adults (p<0.001 in each case). Influenza virus- and M tuberculosis-specific CD4+ T cell responses in BAL were impaired in HIV-infected individuals: proportions of total antigen-specific CD4+ T cells and of polyfunctional IFN-γ and TNF-α-secreting cells were lower in HIV-infected individuals than in HIV-uninfected adults (p<0.05 in each case).ConclusionsBAL antigen-specific CD4+ T cell responses against important viral and bacterial respiratory pathogens are impaired in HIV-infected adults. This might contribute to the susceptibility of HIV-infected adults to lower respiratory tract infections such as pneumonia and tuberculosis.

Asymptomatic HIV-infected Individuals on Antiretroviral Therapy Exhibit Impaired Lung CD4+T-Cell Responses to Mycobacteria

“…However, given the invasive nature and the associated risk of bronchoscopy, especially in HIV-infected persons, a longitudinal study was judged not to be justifiable. Furthermore, the alveolar lymphocyte counts from HIV-uninfected individuals were higher than has been reported previously (4,5,40). Household indoor air pollution is highly prevalent in Malawi (41) and it is possible that this group of individuals had ongoing alveolar inflammation.…”

“…In high transmission regions, most TB cases in HIV-individuals result from recent Mycobacterium tuberculosis (Mtb) infection indicating that in these individuals the lung is more permissive for the establishment or progression of primary infections (3). Recent studies have reported that alveolar macrophage (AM) proteolytic function and mycobacterial antigen-specific Th1 CD4 1 T-cell responses in the lung are impaired in asymptomatic HIV-infected, antiretroviral therapy (ART)-naive persons (4)(5)(6). These findings indicate that HIV alters both innate and adaptive immunity in the lung to render HIV-infected individuals incapable of mounting adequate pulmonary immune responses to control Mtb.…”

“…Collection and Processing of BAL and Blood Samples BAL samples were collected at bronchoscopy and processed as previously described (5,12). AM were isolated from BAL cells by adherence to plastic (6) and adherent cells were used for assessment of AM phagosomal proteolysis; nonadherent BAL cells, which were predominantly lymphocytes, were used to assess intracellular cytokine production by alveolar CD4 1 T cells.…”

Korelasi Jumlah Cluster of Differentiation 4 dengan Jenis Bakteri Penyebab Infeksi Paru dari Kultur Bilasan Bronkoalveolar pada Pasien Human Immunodeficiency Virus

“…4 Kemampuan mikroorganisme menginfeksi paru-paru tidak hanya bergantung pada suatu patogenisitasnya, tetapi juga pada kemampuan mikroorganisme untuk mengatasi kekebalan tubuh tuan rumah. Infeksi HIV mengakibatkan penurunan kuantitatif dan juga kualitatif cluster of differentiation 4 (CD4) limfosit T. 5 Delapan puluh persen kasus pneumonia bakteri terjadi pada kondisi CD4 <400 sel/mm 3 dan pneumonia bakteri terbanyak terjadi pada CD4 <200 sel/ mm 3 . 6 Jenis bakteri gram positif yang menyebabkan infeksi paru tersering pada populasi HIV adalah Streptococcus pneumoniae (S. pneumoniae).…”

Respiratory Infection and the Impact of Pulmonary Immunity on Lung Health and Disease

“…Adult humans without ongoing infections have tremendous numbers of T cells residing in their lungs, equivalent to the total numbers in the blood (42). T cells in the lungs, nasal tissues, and blood of adults without ongoing infections respond to respiratory pathogens, such as pneumococcus and influenza, with greater responsiveness by T cells from the relevant tissues, suggesting a mucosal compartmentalization of immunity (42)(43)(44)(45). Respiratory pathogen-reactive T cells often generate IL-17 on stimulation (42,45), consistent with an ability to amplify neutrophil-mediated host defense in the lungs.…”