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

Jambo, Kondwani ORCID: https://orcid.org/0000-0002-3195-2210, Sepako, Enoch, Fullerton, Duncan, Mzinza, David, Glennie, Sarah, Wright, Adam, Heyderman, Robert and Gordon, Stephen ORCID: https://orcid.org/0000-0001-6576-1116 (2011) 'Bronchoalveolar CD4+ T cell responses to respiratory antigens are impaired in HIV-infected adults'. Thorax, Vol 66, pp. 375-382.

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Abstract

Rationale

HIV-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.

Objective

To 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.

Methods

We 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 results

CD4+ 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).

Conclusions

BAL 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.

Item Type:	Article
Additional Information:	The original electronic version is published at: http://thorax.bmj.com/content/66/5/375
Subjects:	WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503.5 Complications WF Respiratory System > WF 140 Diseases of the respiratory system (General)
Digital Object Identifer (DOI):	https://doi.org/10.1136/thx.2010.153825
Depositing User:	Users 43 not found.
Date Deposited:	11 Jul 2011 09:32
Last Modified:	07 Jun 2022 11:09
URI:	https://archive.lstmed.ac.uk/id/eprint/2088

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