Source:http://linkedlifedata.com/resource/pubmed/id/21813616
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
19
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pubmed:dateCreated |
2011-9-12
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pubmed:abstractText |
Percentages of activated T cells correlate with HIV-1 disease progression, but the underlying mechanisms are not fully understood. We hypothesized that HLA-DR(+) CD38(+) (DR(+) 38(+)) CD4(+) T cells produce the majority of HIV-1 due to elevated expression of CCR5 and CXCR4. In phytohemagglutinin (PHA)-stimulated CD8-depleted peripheral blood mononuclear cells (PBMC) infected with HIV-1 green fluorescent protein (GFP) reporter viruses, DR(-) 38(+) T cells constituted the majority of CCR5 (R5)-tropic (median, 62%) and CXCR4 (X4)-tropic HIV-1-producing cells (median, 61%), although cell surface CCR5 and CXCR4 were not elevated in this subset of cells. In lymph nodes from untreated individuals infected with R5-tropic HIV-1, percentages of CCR5(+) cells were elevated in DR(+) 38(+) CD4(+) T cells (median, 36.4%) compared to other CD4(+) T-cell subsets (median values of 5.7% for DR(-) 38(-) cells, 19.4% for DR(+) 38(-) cells, and 7.6% for DR(-) 38(+) cells; n = 18; P < 0.001). In sorted CD8(-) lymph node T cells, median HIV-1 RNA copies/10(5) cells was higher for DR(+) 38(+) cells (1.8 × 10(6)) than for DR(-) 38(-) (0.007 × 10(6)), DR(-) 38(+) (0.064 × 10(6)), and DR(+) 38(-) (0.18 × 10(6)) subsets (n = 8; P < 0.001 for all). After adjusting for percentages of subsets, a median of 87% of viral RNA was harbored by DR(+) 38(+) cells. Percentages of CCR5(+) CD4(+) T cells and concentrations of CCR5 molecules among subsets predicted HIV-1 RNA levels among CD8(-) DR/38 subsets (P < 0.001 for both). Median HIV-1 DNA copies/10(5) cells was higher in DR(+) 38(+) cells (5,360) than in the DR(-) 38(-) (906), DR(-) 38(+) (814), and DR(+) 38(-) (1,984) subsets (n = 7; P ? 0.031). Thus, DR(+) 38(+) CD4(+) T cells in lymph nodes have elevated CCR5 expression, are highly susceptible to infection with R5-tropic virus, and produce the majority of R5-tropic HIV-1. PBMC assays failed to recapitulate in vivo findings, suggesting limited utility. Strategies to reduce numbers of DR(+) 38(+) CD4(+) T cells may substantially inhibit HIV-1 replication.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD38,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD4,
http://linkedlifedata.com/resource/pubmed/chemical/CD38 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/HLA-DR Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Viral,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, CCR5,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, HIV
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1098-5514
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pubmed:author |
pubmed-author:CampbellThomas BTB,
pubmed-author:CoakleyEoinE,
pubmed-author:ConnickElizabethE,
pubmed-author:FolkvordJoy MJM,
pubmed-author:HaasMichelle KMK,
pubmed-author:LevyDavid NDN,
pubmed-author:LieYolandaY,
pubmed-author:MawhinneySamanthaS,
pubmed-author:McCarterMartinM,
pubmed-author:MeditzAmie LAL,
pubmed-author:MelanderKelseyK,
pubmed-author:YoungRussR
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pubmed:issnType |
Electronic
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pubmed:volume |
85
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
10189-200
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pubmed:meshHeading |
pubmed-meshheading:21813616-Adult,
pubmed-meshheading:21813616-Antigens, CD38,
pubmed-meshheading:21813616-Antigens, CD4,
pubmed-meshheading:21813616-Female,
pubmed-meshheading:21813616-HIV-1,
pubmed-meshheading:21813616-HLA-DR Antigens,
pubmed-meshheading:21813616-Humans,
pubmed-meshheading:21813616-Lymph Nodes,
pubmed-meshheading:21813616-Male,
pubmed-meshheading:21813616-Membrane Glycoproteins,
pubmed-meshheading:21813616-Middle Aged,
pubmed-meshheading:21813616-RNA, Viral,
pubmed-meshheading:21813616-Receptors, CCR5,
pubmed-meshheading:21813616-Receptors, HIV,
pubmed-meshheading:21813616-T-Lymphocyte Subsets
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pubmed:year |
2011
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pubmed:articleTitle |
HLA-DR+ CD38+ CD4+ T lymphocytes have elevated CCR5 expression and produce the majority of R5-tropic HIV-1 RNA in vivo.
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pubmed:affiliation |
Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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