PMID- 21880771
OWN - NLM
STAT- MEDLINE
DCOM- 20111121
LR  - 20211020
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 85
IP  - 21
DP  - 2011 Nov
TI  - Increased frequency of regulatory T cells accompanies increased immune activation 
      in rectal mucosae of HIV-positive noncontrollers.
PG  - 11422-34
LID - 10.1128/JVI.05608-11 [doi]
AB  - Gut-associated lymphoid tissue (GALT) is a major site of HIV replication and 
      CD4(+) T cell depletion. Furthermore, microbial translocation facilitated by 
      mucosal damage likely contributes to the generalized immune activation observed 
      in HIV infection. Regulatory T cells (Treg) help maintain homeostasis and 
      suppress harmful immune activation during infection; however, in the case of 
      persistent viral infections such as HIV, their role is less clear. Although a 
      number of studies have examined Treg in blood during chronic infection, few have 
      explored Treg in the gastrointestinal mucosa. For this study, paired blood and 
      rectal biopsy samples were obtained from 12 HIV noncontrollers (viral load of 
      >10,000 copies/ml plasma), 10 HIV controllers (viral load of <500 copies/ml 
      plasma for more than 5 years), and 12 HIV seronegative control subjects. 
      Noncontrollers had significantly higher percentages of Treg in rectal mononuclear 
      cells (RMNC), but not in blood, compared to seronegative subjects (P = 0.001) or 
      HIV controllers (P = 0.002). Mucosal Treg positively correlated with viral load 
      (P = 0.01) and expression of immune activation markers by CD4(+) (P = 0.01) and 
      CD8(+) (P = 0.07) T cells. Suppression assays indicated that mucosal and 
      peripheral Treg of noncontrollers and controllers maintained their capacity to 
      suppress non-Treg proliferation to a similar extent as Treg from seronegative 
      subjects. Together, these findings reveal that rather than experiencing 
      depletion, mucosal Treg frequency is enhanced during chronic HIV infection and is 
      positively correlated with viral load and immune activation. Moreover, mucosal 
      Treg maintain their suppressive ability during chronic HIV infection, potentially 
      contributing to diminished HIV-specific T cell responses and viral persistence.
FAU - Shaw, Julia M
AU  - Shaw JM
AD  - Department of Medical Microbiology and Immunology, School of Medicine, University 
      of California-Davis, 1 Shields Ave., Davis, CA 95616, USA.
FAU - Hunt, Peter W
AU  - Hunt PW
FAU - Critchfield, J William
AU  - Critchfield JW
FAU - McConnell, Delandy H
AU  - McConnell DH
FAU - Garcia, Juan Carlos
AU  - Garcia JC
FAU - Pollard, Richard B
AU  - Pollard RB
FAU - Somsouk, Ma
AU  - Somsouk M
FAU - Deeks, Steven G
AU  - Deeks SG
FAU - Shacklett, Barbara L
AU  - Shacklett BL
LA  - eng
GR  - R24-AI067039/AI/NIAID NIH HHS/United States
GR  - R01-AI057020/AI/NIAID NIH HHS/United States
GR  - P01 AI076174/AI/NIAID NIH HHS/United States
GR  - K23 CA157929/CA/NCI NIH HHS/United States
GR  - C06-RR012088/RR/NCRR NIH HHS/United States
GR  - K24 AI069994/AI/NIAID NIH HHS/United States
GR  - UL1 RR024131/RR/NCRR NIH HHS/United States
GR  - R01 AI087145/AI/NIAID NIH HHS/United States
GR  - UL1-RR024131/RR/NCRR NIH HHS/United States
GR  - P01-AI027763/AI/NIAID NIH HHS/United States
GR  - R01-AI076174/AI/NIAID NIH HHS/United States
GR  - R24 AI067039/AI/NIAID NIH HHS/United States
GR  - R01-AI087145/AI/NIAID NIH HHS/United States
GR  - P30 AI027763/AI/NIAID NIH HHS/United States
GR  - R01 AI057020/AI/NIAID NIH HHS/United States
GR  - K24-AI069994/AI/NIAID NIH HHS/United States
GR  - C06 RR012088/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110831
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Antigens, CD)
SB  - IM
MH  - Antigens, CD/analysis
MH  - Blood/immunology/virology
MH  - CD4-Positive T-Lymphocytes/chemistry/immunology
MH  - CD8-Positive T-Lymphocytes/chemistry/immunology
MH  - HIV Infections/*immunology
MH  - *Immunity, Mucosal
MH  - Intestinal Mucosa/*immunology/virology
MH  - Rectum/*immunology/virology
MH  - T-Lymphocyte Subsets/chemistry/immunology
MH  - T-Lymphocytes, Regulatory/chemistry/*immunology
MH  - Viral Load
PMC - PMC3194952
EDAT- 2011/09/02 06:00
MHDA- 2011/12/13 00:00
PMCR- 2012/05/01
CRDT- 2011/09/02 06:00
PHST- 2011/09/02 06:00 [entrez]
PHST- 2011/09/02 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
PHST- 2012/05/01 00:00 [pmc-release]
AID - JVI.05608-11 [pii]
AID - 5608-11 [pii]
AID - 10.1128/JVI.05608-11 [doi]
PST - ppublish
SO  - J Virol. 2011 Nov;85(21):11422-34. doi: 10.1128/JVI.05608-11. Epub 2011 Aug 31.