Author | Hsu, Denise C | |
Author | Breglio, Kimberly F | |
Author | Pei, Luxin | |
Author | Wong, Chun-Shu | |
Author | Andrade, Bruno de Bezerril | |
Author | Sheikh, Virginia | |
Author | Smelkinson, Margery | |
Author | Petrovas, Constantinos | |
Author | Rupert, Adam | |
Author | Santana, Leonardo Gil | |
Author | Zelazny, Adrian | |
Author | Holland, Steven M | |
Author | Olivier, Kenneth | |
Author | Barber, Daniel | |
Author | Sereti, Irini | |
Access date | 2018-04-18T13:17:51Z | |
Available date | 2018-04-18T13:17:51Z | |
Document date | 2018 | |
Citation | HSU, D. C. et al. Emergence of Polyfunctional Cytotoxic CD4+ T Cells in Mycobacterium avium Immune Reconstitution Inflammatory Syndrome in Human Immunodeficiency Virus-Infected Patients. Clinical Infectious Diseases, 2018. | pt_BR |
ISSN | 1058-4838 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/25926 | |
Description | Andrade, Bruno de Bezerril. Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. 1Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland; 2Instituto Gonçalo Moniz, Fundação
Oswaldo Cruz, 3Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative, Fundação José Silveira, and 4Curso de Medicina, Faculdade de Tecnologia
e Ciências, Salvador, Bahia, Brazil; 5Wellcome Centre for Infectious Disease Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa;
6Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee; 7Biological Imaging Section, NIAID and 8Tissue Analysis Core Section,
Vaccine Research Center, NIAID, NIH, Bethesda, Maryland; 9Functional Immunology Section, AIDS Monitoring Laboratory, SAIC-Frederick, National Cancer Institute, National Institutes of Health,
Frederick, Maryland; and 10Department of Laboratory Medicine, 11Laboratory of Clinical Infectious Diseases, NIAID, 12Pulmonary Clinical Medicine Section, National Heart, Lung, and Blood
Institute, and 13Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, Maryland | pt_BR |
Sponsorship | Intramural Research Program of the NIAID at the NIH. | pt_BR |
Language | eng | pt_BR |
Publisher | Oxford University Press | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Síndrome inflamatória de reconstituição imune | pt_BR |
Subject in Portuguese | ÍRIS | pt_BR |
Subject in Portuguese | Complexo Mycobacterium avium | pt_BR |
Subject in Portuguese | MAC | pt_BR |
Subject in Portuguese | HIV | pt_BR |
Title | Emergence of Polyfunctional Cytotoxic CD4+ T Cells in Mycobacterium avium Immune Reconstitution Inflammatory Syndrome in Human Immunodeficiency Virus-Infected Patients | pt_BR |
Type | Article | pt_BR |
DOI | 10.1093/cid/ciy016 | |
Abstract | Immune reconstitution inflammatory syndrome (IRIS) is an aberrant inflammatory response in individuals with advanced human immunodeficiency virus (HIV) infection, after antiretroviral therapy (ART) initiation. The pathogenesis of Mycobacterium avium complex (MAC)-associated IRIS has not been fully elucidated. Methods. We investigated monocyte and CD4+ T-cell responses in vitro, tumor necrosis factor (TNF) expression in tissues, and
plasma cytokines and inflammatory markers, in 13 HIV-infected patients with MAC-IRIS and 14 HIV-uninfected patients with
pulmonary MAC infection.
Results. Prior to ART, HIV-infected compared with HIV-uninfected patients, had reduced TNF+ monocytes (P = .013), although
similar cytokine (interferon gamma [IFN-γ], TNF, interleukin 2 [IL-2], and interleukin 17 [IL-17])–expressing CD4+ T cells. During
IRIS, monocyte cytokine production was restored. IFN-γ+ (P = .027), TNF+ (P = .004), and polyfunctional CD4+ T cells (P = 0.03)
also increased. These effectors were T-betlow, and some expressed markers of degranulation and cytotoxic potential. Blockade of
cytotoxic T-lymphocyte associated protein 4 and lymphocyte activation gene-3 further increased CD4+ T-cell cytokine production.
Tissue immunofluorescence showed higher proportions of CD4+ and CD68+ (monocyte/macrophage) cells expressed TNF during
IRIS compared with HIV-uninfected patients. Plasma IFN-γ (P = .048), C-reactive protein (P = .008), and myeloperoxidase (P <
.001) levels also increased, whereas interleukin 10 decreased (P = .008) during IRIS.
Conclusions. Advanced HIV infection was associated with impaired MAC responses. Restoration of monocyte responses and
expansion of polyfunctional MAC-specific T-betlow CD4+ T cells with cytotoxic potential after ART initiation may overwhelm existing
regulatory and inhibitory mechanisms, leading to MAC-IRIS. | pt_BR |
Affilliation | Múltipla – ver em Notas | pt_BR |
Subject | Immune reconstitution inflammatory syndrome | pt_BR |
Subject | IRIS | pt_BR |
Subject | Mycobacterium avium complex | pt_BR |
Subject | MAC | pt_BR |
Subject | HIV | pt_BR |