PMID- 20660788
OWN - NLM
STAT- MEDLINE
DCOM- 20101216
LR  - 20240216
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 116
IP  - 19
DP  - 2010 Nov 11
TI  - Elevated frequencies of highly activated CD4+ T cells in HIV+ patients developing 
      immune reconstitution inflammatory syndrome.
PG  - 3818-27
LID - 10.1182/blood-2010-05-285080 [doi]
AB  - Immune reconstitution inflammatory syndrome (IRIS) is a considerable problem in 
      the treatment of HIV-infected patients. To identify immunologic correlates of 
      IRIS, we characterized T-cell phenotypic markers and serum cytokine levels in HIV 
      patients with a range of different AIDS-defining illnesses, before and at regular 
      time points after initiation of antiretroviral therapy. Patients developing IRIS 
      episodes displayed higher frequencies of effector memory, PD-1(+), HLA-DR(+), and 
      Ki67(+) CD4(+) T cells than patients without IRIS. Moreover, PD-1(+) CD4(+) T 
      cells in IRIS patients expressed increased levels of LAG-3, CTLA-4, and ICOS and 
      had a Th1/Th17 skewed cytokine profile upon polyclonal stimulation. Elevated PD-1 
      and Ki67 expression was also seen in regulatory T cells of IRIS patients. 
      Furthermore, IRIS patients displayed higher serum interferon-gamma, compared with 
      non-IRIS patients, near the time of their IRIS events and higher serum 
      interleukin-7 levels, suggesting that the T-cell populations are also exposed to 
      augmented homeostatic signals. In conclusion, our findings indicate that IRIS 
      appears to be a predominantly CD4-mediated phenomenon with reconstituting 
      effector and regulatory T cells showing evidence of increased activation from 
      antigenic exposure. These studies are registered online at 
      http://clinicaltrials.gov as NCT00557570 and NCT00286767.
FAU - Antonelli, Lis R V
AU  - Antonelli LR
AD  - Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of 
      Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 
      USA.
FAU - Mahnke, Yolanda
AU  - Mahnke Y
FAU - Hodge, Jessica N
AU  - Hodge JN
FAU - Porter, Brian O
AU  - Porter BO
FAU - Barber, Daniel L
AU  - Barber DL
FAU - DerSimonian, Rebecca
AU  - DerSimonian R
FAU - Greenwald, Jamieson H
AU  - Greenwald JH
FAU - Roby, Gregg
AU  - Roby G
FAU - Mican, Joann
AU  - Mican J
FAU - Sher, Alan
AU  - Sher A
FAU - Roederer, Mario
AU  - Roederer M
FAU - Sereti, Irini
AU  - Sereti I
LA  - eng
SI  - ClinicalTrials.gov/NCT00286767
SI  - ClinicalTrials.gov/NCT00557570
GR  - HHSN261200800001C/RC/CCR NIH HHS/United States
GR  - HHSN261200800001E/CA/NCI NIH HHS/United States
GR  - ImNIH/Intramural NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
DEP - 20100726
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Antigens, CD)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Cytokines)
RN  - 0 (PDCD1 protein, human)
RN  - 0 (Programmed Cell Death 1 Receptor)
SB  - IM
MH  - Anti-HIV Agents/*adverse effects
MH  - Antigens, CD/metabolism
MH  - Apoptosis Regulatory Proteins/metabolism
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - Case-Control Studies
MH  - Cytokines/blood
MH  - HIV Infections/*drug therapy/*immunology
MH  - HIV-1
MH  - Humans
MH  - Immune Reconstitution Inflammatory Syndrome/*etiology/*immunology
MH  - Immunologic Memory
MH  - Lymphocyte Activation
MH  - Programmed Cell Death 1 Receptor
MH  - Retrospective Studies
MH  - T-Lymphocyte Subsets/immunology
PMC - PMC2981537
EDAT- 2010/07/28 06:00
MHDA- 2010/12/17 06:00
PMCR- 2011/11/11
CRDT- 2010/07/28 06:00
PHST- 2010/07/28 06:00 [entrez]
PHST- 2010/07/28 06:00 [pubmed]
PHST- 2010/12/17 06:00 [medline]
PHST- 2011/11/11 00:00 [pmc-release]
AID - S0006-4971(20)31105-8 [pii]
AID - 2010/285080 [pii]
AID - 10.1182/blood-2010-05-285080 [doi]
PST - ppublish
SO  - Blood. 2010 Nov 11;116(19):3818-27. doi: 10.1182/blood-2010-05-285080. Epub 2010 
      Jul 26.