PMID- 21189271
OWN - NLM
STAT- MEDLINE
DCOM- 20110414
LR  - 20220419
IS  - 1537-6591 (Electronic)
IS  - 1058-4838 (Print)
IS  - 1058-4838 (Linking)
VI  - 52
IP  - 3
DP  - 2011 Feb 1
TI  - Development of cytomegalovirus (CMV) immune recovery uveitis is associated with 
      Th17 cell depletion and poor systemic CMV-specific T cell responses.
PG  - 409-17
LID - 10.1093/cid/ciq112 [doi]
AB  - BACKGROUND: the immune reconstitution inflammatory syndromes (IRIS) are a 
      spectrum of inflammatory conditions associated with opportunistic infections and 
      occurring in approximately16% of human immunodeficiency type 1 (HIV-1)-infected 
      patients given antiretroviral therapy. It has been proposed that these conditions 
      are linked by a dysregulated immune system that is prone to exaggerated 
      responses. However, immunologic studies have been limited by the availability of 
      longitudinal samples from patients with IRIS and appropriate matched control 
      subjects. Cytomegalovirus (CMV) immune recovery uveitis (IRU) is an IRIS 
      occurring in up to 38% of patients with CMV retinitis. Although the pathologic 
      immune responses occur in the eye, immune dysregulation that allows for 
      development of pathologic responses is presumably caused by faulty systemic 
      immune cell reconstitution. METHODS: we examined CMV-specific T cell responses, 
      regulatory T (T(reg)) cell function and polyclonal T cell responses, including 
      IL-17 production, in 25 patients with CMV IRU and 49 immunorestored control 
      subjects with CMV retinitis who did not develop IRU. RESULTS: patients with CMV 
      IRU had poor CMV-specific CD4(+) T cell responses, as compared with control 
      subjects, whereas CD8(+) T cell responses were comparable. Patients with CMV IRU 
      were characterized by smaller numbers of circulating Th17 cells. Deficiency in 
      anti-CMV responses was not associated with differences in T(reg) cell function. 
      CONCLUSIONS: the T(reg) cell compartment is intact in patients with CMV IRU, and 
      these patients do not develop exaggerated systemic CMV-specific or polyclonal 
      immune responses. Cases are instead characterized by more profound depletion of 
      Th17 cells and poor antiviral immune responses. CMV IRU may be most likely to 
      develop in persons experiencing the greatest degree of immune dysfunction before 
      initiating highly active antiretroviral therapy.
FAU - Hartigan-O'Connor, Dennis J
AU  - Hartigan-O'Connor DJ
AD  - Division of Experimental Medicine, University of California, San Francisco, CA 
      94110, USA. dhartigan@medsfgh.ucsf.edu
FAU - Jacobson, Mark A
AU  - Jacobson MA
FAU - Tan, Qi Xuan
AU  - Tan QX
FAU - Sinclair, Elizabeth
AU  - Sinclair E
CN  - Studies of Ocular Complications of AIDS Research Group
LA  - eng
GR  - P30AI027763/AI/NIAID NIH HHS/United States
GR  - UL1 RR024131/RR/NCRR NIH HHS/United States
GR  - K23 AI081540/AI/NIAID NIH HHS/United States
GR  - P30 AI027763/AI/NIAID NIH HHS/United States
GR  - R21 EY018559/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20101228
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)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Anti-Retroviral Agents/adverse effects/*therapeutic use
MH  - Cytomegalovirus/*immunology/pathogenicity
MH  - Cytomegalovirus Infections/*immunology/pathology/virology
MH  - Female
MH  - HIV Infections/complications/*drug therapy
MH  - Humans
MH  - Immune Reconstitution Inflammatory Syndrome
MH  - Male
MH  - Middle Aged
MH  - T-Lymphocyte Subsets/*immunology
MH  - Th17 Cells/*immunology
MH  - Uveitis/*immunology/virology
PMC - PMC3060886
EDAT- 2010/12/30 06:00
MHDA- 2011/04/16 06:00
PMCR- 2011/02/01
CRDT- 2010/12/30 06:00
PHST- 2010/12/30 06:00 [entrez]
PHST- 2010/12/30 06:00 [pubmed]
PHST- 2011/04/16 06:00 [medline]
PHST- 2011/02/01 00:00 [pmc-release]
AID - ciq112 [pii]
AID - 10.1093/cid/ciq112 [doi]
PST - ppublish
SO  - Clin Infect Dis. 2011 Feb 1;52(3):409-17. doi: 10.1093/cid/ciq112. Epub 2010 Dec 
      28.