|
|
|
|
TIGIT Marks Exhausted T Cells,Correlates with Disease Progression,and Serves as a Target for Immune Restoration in HIV and SIV Infection
|
|
|
|
|
|
|
|
نویسنده
|
chew g.m. ,fujita t. ,webb g.m. ,burwitz b.j. ,wu h.l. ,reed j.s. ,hammond k.b. ,clayton k.l. ,ishii n. ,abdel-mohsen m. ,liegler t. ,mitchell b.i. ,hecht f.m. ,ostrowski m. ,shikuma c.m. ,hansen s.g. ,maurer m. ,korman a.j. ,deeks s.g. ,sacha j.b. ,ndhlovu l.c.
|
|
منبع
|
plos pathogens - 2016 - دوره : 12 - شماره : 1
|
|
چکیده
|
Hiv infection induces phenotypic and functional changes to cd8+ t cells defined by the coordinated upregulation of a series of negative checkpoint receptors that eventually result in t cell exhaustion and failure to control viral replication. we report that effector cd8+ t cells during hiv infection in blood and siv infection in lymphoid tissue exhibit higher levels of the negative checkpoint receptor tigit. increased frequencies of tigit+ and tigit+ pd-1+ cd8+ t cells correlated with parameters of hiv and siv disease progression. tigit remained elevated despite viral suppression in those with either pharmacological antiretroviral control or immunologically in elite controllers. hiv and siv-specific cd8+ t cells were dysfunctional and expressed high levels of tigit and pd-1. ex-vivo single or combinational antibody blockade of tigit and/or pd-l1 restored viral-specific cd8+ t cell effector responses. the frequency of tigit+ cd4+ t cells correlated with the cd4+ t cell total hiv dna. these findings identify tigit as a novel marker of dysfunctional hiv-specific t cells and suggest tigit along with other checkpoint receptors may be novel curative hiv targets to reverse t cell exhaustion. © 2016 chew et al.
|
|
|
|
|
آدرس
|
hawaii center for hiv/aids,department of tropical medicine,john a. burns school of medicine,university of hawaii,honolulu,hi, United States, hawaii center for hiv/aids,department of tropical medicine,john a. burns school of medicine,university of hawaii,honolulu,hi,united states,department of microbiology and immunology,tohoku university graduate school of medicine,sendai, Japan, vaccine and gene therapy institute,oregon health and science university,portland,or,united states,oregon national primate research center,oregon health and science university,portland,or, United States, vaccine and gene therapy institute,oregon health and science university,portland,or,united states,oregon national primate research center,oregon health and science university,portland,or, United States, vaccine and gene therapy institute,oregon health and science university,portland,or,united states,oregon national primate research center,oregon health and science university,portland,or, United States, vaccine and gene therapy institute,oregon health and science university,portland,or,united states,oregon national primate research center,oregon health and science university,portland,or, United States, vaccine and gene therapy institute,oregon health and science university,portland,or,united states,oregon national primate research center,oregon health and science university,portland,or, United States, department of immunology,university of toronto,toronto,on, Canada, department of microbiology and immunology,tohoku university graduate school of medicine,sendai, Japan, division of experimental medicine,department of medicine,san francisco general hospital,university of california,san francisco,san francisco,ca, United States, division of experimental medicine,department of medicine,san francisco general hospital,university of california,san francisco,san francisco,ca, United States, hawaii center for hiv/aids,department of tropical medicine,john a. burns school of medicine,university of hawaii,honolulu,hi, United States, hiv/aids division,department of medicine,san francisco general hospital,university of california,san francisco,san francisco,ca, United States, department of immunology,university of toronto,toronto,on, Canada, hawaii center for hiv/aids,department of tropical medicine,john a. burns school of medicine,university of hawaii,honolulu,hi, United States, vaccine and gene therapy institute,oregon health and science university,portland,or,united states,oregon national primate research center,oregon health and science university,portland,or, United States, biologics discovery california,bristol-myers squibb,redwood city,ca, United States, biologics discovery california,bristol-myers squibb,redwood city,ca, United States, hiv/aids division,department of medicine,san francisco general hospital,university of california,san francisco,san francisco,ca, United States, vaccine and gene therapy institute,oregon health and science university,portland,or,united states,oregon national primate research center,oregon health and science university,portland,or, United States, hawaii center for hiv/aids,department of tropical medicine,john a. burns school of medicine,university of hawaii,honolulu,hi, United States
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Authors
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|