PMID- 29538651
OWN - NLM
STAT- MEDLINE
DCOM- 20191104
LR  - 20191104
IS  - 1537-6591 (Electronic)
IS  - 1058-4838 (Print)
IS  - 1058-4838 (Linking)
VI  - 67
IP  - 3
DP  - 2018 Jul 18
TI  - Emergence of Polyfunctional Cytotoxic CD4+ T Cells in Mycobacterium avium Immune 
      Reconstitution Inflammatory Syndrome in Human Immunodeficiency Virus-Infected 
      Patients.
PG  - 437-446
LID - 10.1093/cid/ciy016 [doi]
AB  - BACKGROUND: 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-gamma], TNF, interleukin 2 
      [IL-2], and interleukin 17 [IL-17])-expressing CD4+ T cells. During IRIS, 
      monocyte cytokine production was restored. IFN-gamma+ (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-gamma (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.
FAU - Hsu, Denise C
AU  - Hsu DC
AD  - Laboratory of Immunoregulation, National Institute of Allergy and Infectious 
      Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland.
FAU - Breglio, Kimberly F
AU  - Breglio KF
AD  - Laboratory of Immunoregulation, National Institute of Allergy and Infectious 
      Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland.
FAU - Pei, Luxin
AU  - Pei L
AD  - Laboratory of Immunoregulation, National Institute of Allergy and Infectious 
      Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland.
FAU - Wong, Chun-Shu
AU  - Wong CS
AD  - Laboratory of Immunoregulation, National Institute of Allergy and Infectious 
      Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland.
FAU - Andrade, Bruno B
AU  - Andrade BB
AD  - Instituto Goncalo Moniz, Fundacao Oswaldo Cruz, Salvador, Bahia, Brazil.
AD  - Multinational Organization Network Sponsoring Translational and Epidemiological 
      Research Initiative, Fundacao Jose Silveira, Salvador, Bahia, Brazil.
AD  - Curso de Medicina, Faculdade de Tecnologia e Ciencias, Salvador, Bahia, Brazil.
AD  - Wellcome Centre for Infectious Disease Research in Africa, Institute of 
      Infectious Disease and Molecular Medicine, University of Cape Town, South Africa.
AD  - Division of Infectious Diseases, Department of Medicine, Vanderbilt University 
      School of Medicine, Nashville, Tennessee.
FAU - Sheikh, Virginia
AU  - Sheikh V
AD  - Laboratory of Immunoregulation, National Institute of Allergy and Infectious 
      Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland.
FAU - Smelkinson, Margery
AU  - Smelkinson M
AD  - Biological Imaging Section, NIAID, Bethesda, Maryland.
FAU - Petrovas, Constantinos
AU  - Petrovas C
AD  - Tissue Analysis Core Section, Vaccine Research Center, NIAID, NIH, Bethesda, 
      Maryland.
FAU - Rupert, Adam
AU  - Rupert A
AD  - Functional Immunology Section, AIDS Monitoring Laboratory, SAIC-Frederick, 
      National Cancer Institute, National Institutes of Health, Frederick, Maryland.
FAU - Gil-Santana, Leonardo
AU  - Gil-Santana L
AD  - Instituto Goncalo Moniz, Fundacao Oswaldo Cruz, Salvador, Bahia, Brazil.
AD  - Multinational Organization Network Sponsoring Translational and Epidemiological 
      Research Initiative, Fundacao Jose Silveira, Salvador, Bahia, Brazil.
AD  - Curso de Medicina, Faculdade de Tecnologia e Ciencias, Salvador, Bahia, Brazil.
FAU - Zelazny, Adrian
AU  - Zelazny A
AD  - Department of Laboratory Medicine, NIAID, NIH, Bethesda, Maryland.
FAU - Holland, Steven M
AU  - Holland SM
AD  - Laboratory of Clinical Infectious Diseases, NIAID Bethesda, Maryland.
FAU - Olivier, Kenneth
AU  - Olivier K
AD  - Pulmonary Clinical Medicine Section, National Heart, Lung, and Blood Institute.
FAU - Barber, Daniel
AU  - Barber D
AD  - Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, Maryland.
FAU - Sereti, Irini
AU  - Sereti I
AD  - Laboratory of Immunoregulation, National Institute of Allergy and Infectious 
      Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland.
LA  - eng
GR  - HHMI/Howard Hughes Medical Institute/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Infect Dis
JT  - Clinical infectious diseases : an official publication of the Infectious Diseases 
      Society of America
JID - 9203213
RN  - 0 (Cytokines)
SB  - IM
MH  - Adult
MH  - Aged
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - Cohort Studies
MH  - Cytokines/immunology
MH  - Female
MH  - HIV Infections/*complications/*immunology/microbiology
MH  - Humans
MH  - Immune Reconstitution Inflammatory Syndrome/immunology/*microbiology/virology
MH  - Male
MH  - Middle Aged
MH  - Mycobacterium avium
MH  - T-Lymphocytes, Cytotoxic/*immunology
PMC - PMC6248720
EDAT- 2018/03/15 06:00
MHDA- 2019/11/05 06:00
PMCR- 2019/08/01
CRDT- 2018/03/15 06:00
PHST- 2017/10/04 00:00 [received]
PHST- 2018/02/02 00:00 [accepted]
PHST- 2018/03/15 06:00 [pubmed]
PHST- 2019/11/05 06:00 [medline]
PHST- 2018/03/15 06:00 [entrez]
PHST- 2019/08/01 00:00 [pmc-release]
AID - 4925763 [pii]
AID - ciy016 [pii]
AID - 10.1093/cid/ciy016 [doi]
PST - ppublish
SO  - Clin Infect Dis. 2018 Jul 18;67(3):437-446. doi: 10.1093/cid/ciy016.