Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=27430272
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Cooperation of PD-1 and LAG-3 Contributes to T-Cell Exhaustion in Anaplasma
marginale-Infected Cattle
#MMPMID27430272
Okagawa T
; Konnai S
; Deringer JR
; Ueti MW
; Scoles GA
; Murata S
; Ohashi K
; Brown WC
Infect Immun
2016[Oct]; 84
(10
): 2779-90
PMID27430272
show ga
The CD4(+) T-cell response is central for the control of Anaplasma marginale
infection in cattle. However, the infection induces a functional exhaustion of
antigen-specific CD4(+) T cells in cattle immunized with A. marginale outer
membrane proteins or purified outer membranes (OMs), which presumably facilitates
the persistence of this rickettsia. In the present study, we hypothesize that
T-cell exhaustion following infection is induced by the upregulation of
immunoinhibitory receptors on T cells, such as programmed death 1 (PD-1) and
lymphocyte activation gene 3 (LAG-3). OM-specific T-cell responses and the
kinetics of PD-1-positive (PD-1(+)) LAG-3(+) exhausted T cells were monitored in
A. marginale-challenged cattle previously immunized with OMs. Consistent with
data from previous studies, OM-specific proliferation of peripheral blood
mononuclear cells (PBMCs) and interferon gamma (IFN-?) production were
significantly suppressed in challenged animals by 5 weeks postinfection (wpi). In
addition, bacteremia and anemia also peaked in these animals at 5 wpi. Flow
cytometric analysis revealed that the percentage of PD-1(+) LAG-3(+) T cells in
the CD4(+), CD8(+), and ?? T-cell populations gradually increased and also peaked
at 5 wpi. A large increase in the percentage of LAG-3(+) ?? T cells was also
observed. Importantly, in vitro, the combined blockade of the PD-1 and LAG-3
pathways partially restored OM-specific PBMC proliferation and IFN-? production
at 5 wpi. Taken together, these results indicate that coexpression of PD-1 and
LAG-3 on T cells contributes to the rapid exhaustion of A. marginale-specific T
cells following infection and that these immunoinhibitory receptors regulate
T-cell responses during bovine anaplasmosis.
|Anaplasma marginale/*immunology
[MESH]
|Anaplasmosis/immunology/*microbiology/prevention & control
[MESH]
free
free
free
