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

Jambo, Kondwani ORCID: https://orcid.org/0000-0002-3195-2210, Banda, Dominic H., Afran, Louise, Kankwatira, Anstead M., Malamba, Rose D., Allain, Theresa J., Gordon, Stephen ORCID: https://orcid.org/0000-0001-6576-1116, Heyderman, Robert, Russell, David G. and Mwandumba, Henry ORCID: https://orcid.org/0000-0003-4470-3608 (2014) 'Asymptomatic HIV-infected Individuals on Antiretroviral Therapy Exhibit Impaired Lung CD4+T-Cell Responses to Mycobacteria'. American Journal of Respiratory and Critical Care Medicine, Vol 190, Issue 8, pp. 938-947.

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Abstract

Rationale: HIV-infected persons on antiretroviral therapy (ART) remain at higher risk of pulmonary tuberculosis (TB) than HIV-uninfected individuals. This increased susceptibility may be caused by impairment of alveolar macrophage (AM) function and/or mycobacteria-specific alveolar CD4+ T-cell responses observed in HIV-infected ART-naive adults.

Objectives: To determine whether ART was associated with improvement in both AM function, assessed by phagosomal proteolysis, and alveolar CD4+ T-cell responses to Mycobacterium in HIV-infected individuals.

Methods: Peripheral blood was drawn and bronchoalveolar lavage (BAL) performed on healthy, 35 HIV-uninfected, 25 HIV-infected ART-naive, and 50 HIV-infected ART-treated asymptomatic adults. Phagosomal proteolysis of AM was assessed with fluorogenic beads. Mycobacteria-specific CD4+ T-cell responses were measured by intracellular cytokine staining.

Measurements and Main Results: HIV-infected adults on ART exhibited lower plasma HIV viral load and higher blood CD4+ T-cell count than ART-naive adults. AM proteolysis and total mycobacteria-specific Th1 CD4+ T-cell responses in individuals on ART for greater than or equal to 4 years were similar to HIV-uninfected control subjects but those on ART for less than 4 years had impaired responses. Total influenza-specific alveolar Th1 CD4+ T-cell responses were intact in all individuals receiving ART. In contrast, BAL and blood mycobacteria-specific polyfunctional CD4+ T-cell responses were impaired in adults on ART irrespective of duration.

Conclusions: AM and mycobacteria-specific alveolar CD4+ T-cell responses in HIV-infected adults on ART for less than 4 years are impaired and may partly explain the high risk of TB in HIV-infected individuals on ART. Strategies to augment ART to improve lung immune cell function and reduce the high incidence of TB in HIV-infected adults who initiate ART should be investigated.

Item Type:	Article
Subjects:	QU Biochemistry > Cells and Genetics > QU 375 Cell physiology QW Microbiology and Immunology > Bacteria > QW 125 Actinibacteria, Actinomycetales. WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503 Acquired immunodeficiency syndrome. HIV infections WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503.2 Therapy WF Respiratory System > Tuberculosis > WF 200 Tuberculosis (General)
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1164/rccm.201405-0864OC
Depositing User:	Lynn Roberts-Maloney
Date Deposited:	29 Jan 2015 10:05
Last Modified:	07 Oct 2019 08:24
URI:	https://archive.lstmed.ac.uk/id/eprint/4809

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