PMID- 23645847
OWN - NLM
STAT- MEDLINE
DCOM- 20140207
LR  - 20211021
IS  - 1537-6591 (Electronic)
IS  - 1058-4838 (Linking)
VI  - 57
IP  - 4
DP  - 2013 Aug
TI  - Skewing of the CD4(+) T-cell pool toward monofunctional antigen-specific 
      responses in patients with immune reconstitution inflammatory syndrome in The 
      Gambia.
PG  - 594-603
LID - 10.1093/cid/cit285 [doi]
AB  - BACKGROUND: A common complication of starting antiretroviral therapy (ART) for 
      human immunodeficiency virus (HIV) is the development of immune reconstitution 
      inflammatory syndrome (IRIS) in approximately 25% of patients. Despite 
      similarities with paradoxical reactions to tuberculosis and reversal reactions in 
      leprosy, the exact mechanisms, and therefore potential determinants, of IRIS are 
      still unknown. METHODS: In this longitudinal cohort study, we analyzed 20 
      patients who developed IRIS following initiation of ART and 16 patients who did 
      not, matched for ART time point. Peripheral blood mononuclear cells were 
      stimulated overnight with a positive control antigen and 2 tuberculosis-specific 
      antigens (purified protein derivative [PPD] and ESAT-6/CFP10), followed by 
      polychromatic flow cytometry for analysis of cytokine production from CD4(+) and 
      CD8(+) T cells. RESULTS: Responses to PPD were significantly higher in IRIS 
      patients compared to controls during the IRIS time point, but CD4(+) and CD8(+) 
      T-cell responses to the positive control stimulation were significantly lower in 
      IRIS patients at all time points. Furthermore, whereas control patients had 
      rejuvenated polyfunctional T-cell responses by 3 months after ART, IRIS patients 
      were strikingly monofunctional (generally interferon gamma alone), even up to 6 
      months of ART in response to all stimulations. CONCLUSIONS: Our findings suggest 
      that the peripheral T-cell responses to the underlying pathogen are exaggerated 
      in IRIS patients but that the overall quality of the peripheral T-cell pool is 
      significantly reduced compared to non-IRIS patients. Furthermore, these effects 
      are apparent at least up to 3 months after cessation of IRIS.
FAU - Wilson, Harry
AU  - Wilson H
AD  - Vaccinology Theme, Medical Research Council Unit, Fajara, The Gambia.
FAU - de Jong, Bouke C
AU  - de Jong BC
FAU - Peterson, Kevin
AU  - Peterson K
FAU - Jaye, Assan
AU  - Jaye A
FAU - Kampmann, Beate
AU  - Kampmann B
FAU - Ota, Martin O C
AU  - Ota MO
FAU - Sutherland, Jayne S
AU  - Sutherland JS
LA  - eng
GR  - MC_U190071468/MRC_/Medical Research Council/United Kingdom
GR  - MC_U190085855/MRC_/Medical Research Council/United Kingdom
GR  - MC_UP_A900_1122/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130503
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 (Anti-Retroviral Agents)
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Bacterial Proteins)
RN  - 0 (Cytokines)
RN  - 0 (ESAT-6 protein, Mycobacterium tuberculosis)
RN  - 0 (Tuberculin)
SB  - IM
MH  - Adult
MH  - Anti-Retroviral Agents/adverse effects/*therapeutic use
MH  - Antigens, Bacterial/immunology
MH  - Bacterial Proteins/immunology
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Cohort Studies
MH  - Cytokines/biosynthesis
MH  - Female
MH  - Flow Cytometry
MH  - Gambia
MH  - HIV Infections/complications/*drug therapy/immunology
MH  - Humans
MH  - Immune Reconstitution Inflammatory Syndrome/*immunology
MH  - Leukocytes, Mononuclear
MH  - Longitudinal Studies
MH  - Male
MH  - T-Lymphocyte Subsets/*immunology
MH  - Tuberculin/immunology
MH  - Tuberculosis/*immunology
OTO - NOTNLM
OT  - HIV
OT  - West Africa
OT  - immune reconstitution inflammatory syndrome
OT  - polyfunctional T cells
OT  - tuberculosis
EDAT- 2013/05/07 06:00
MHDA- 2014/02/08 06:00
CRDT- 2013/05/07 06:00
PHST- 2013/05/07 06:00 [entrez]
PHST- 2013/05/07 06:00 [pubmed]
PHST- 2014/02/08 06:00 [medline]
AID - cit285 [pii]
AID - 10.1093/cid/cit285 [doi]
PST - ppublish
SO  - Clin Infect Dis. 2013 Aug;57(4):594-603. doi: 10.1093/cid/cit285. Epub 2013 May 
      3.