Journal article
Regulatory B cell frequency correlates with markers of HIV disease progression and attenuates anti-HIV CD8+ T cell function in vitro
Journal of leukocyte biology, Vol.93(5), pp.811-818
05/2013
DOI: 10.1189/jlb.0912436
PMCID: PMC3629440
PMID: 23434518
Abstract
A role for regulatory B cells is shown in HIV-pathogenesis, potentially impacting HIV cell-mediated control.
HIV infection is associated with elevated expression of IL-10 and PD-L1, contributing to impairment of T cell effector functions. In autoimmunity, tumor immunology, and some viral infections, Bregs modulate T cell function via IL-10 production. In this study, we tested the hypothesis that during HIV infection, Bregs attenuate CD8
+
T cell effector function, contributing to immune dysfunction. We determined that in vitro, TLR2-, TLR9-, and CD40L-costimulated Bregs from HIV
−
individuals exhibited a high frequency of cells expressing IL-10 and PD-L1. Compared with Bregs from HIV
−
individuals, a significantly higher percentage of Bregs from HIV
+
individuals spontaneously expressed IL-10 (
P
=0.0218). After in vitro stimulation with HIV peptides, Breg-depleted PBMCs from HIV
+
individuals exhibited a heightened frequency of cytotoxic (CD107a
+
;
P
=0.0171) and HIV-specific CD8
+
T cells compared with total PBMCs. Furthermore, Breg depletion led to enhanced proliferation of total CD8
+
and CD107a
+
CD8
+
T cells (
P
=0.0280, and
P
=0.0102, respectively). In addition, augmented CD8
+
T cell effector function in vitro was reflected in a 67% increased clearance of infected CD4
+
T cells. The observed Breg suppression of CD8
+
T cell proliferation was IL-10-dependent. In HIV
+
individuals, Breg frequency correlated positively with viral load (
r
=0.4324;
P
=0.0095), immune activation (
r
=0.5978;
P
=0.0005), and CD8
+
T cell exhaustion (CD8
+
PD-1
+
;
r
=0.5893;
P
=0.0101). Finally, the frequency of PD-L1-expressing Bregs correlated positively with CD8
+
PD-1
+
T cells (
r
=0.4791;
P
=0.0443). Our data indicate that Bregs contribute to HIV-infection associated immune dysfunction by T cell impairment, via IL-10 and possibly PD-L1 expression.
Details
- Title: Subtitle
- Regulatory B cell frequency correlates with markers of HIV disease progression and attenuates anti-HIV CD8+ T cell function in vitro
- Creators
- Basile Siewe - Rush University Medical Center, Departments of Immunology/Microbiology and Internal Medicine, Chicago, Illinois, USAJack T Stapleton - Iowa City Veterans Affairs Medical Center and the University of Iowa, Departments of Internal Medicine, Microbiology and Immunology, Iowa City, Iowa, USA; andJeffrey Martinson - Rush University Medical Center, Departments of Immunology/Microbiology and Internal Medicine, Chicago, Illinois, USAAli Keshavarzian - Rush University Medical Center, Departments of Immunology/Microbiology and Internal Medicine, Chicago, Illinois, USANazia Kazmi - Rush University Medical Center, Departments of Immunology/Microbiology and Internal Medicine, Chicago, Illinois, USAPatricia M Demarais - Rush University Medical Center, Departments of Immunology/Microbiology and Internal Medicine, Chicago, Illinois, USAAudrey L French - Rush University Medical Center, Departments of Immunology/Microbiology and Internal Medicine, Chicago, Illinois, USAAlan Landay - Rush University Medical Center, Departments of Immunology/Microbiology and Internal Medicine, Chicago, Illinois, USA
- Resource Type
- Journal article
- Publication Details
- Journal of leukocyte biology, Vol.93(5), pp.811-818
- DOI
- 10.1189/jlb.0912436
- PMID
- 23434518
- PMCID
- PMC3629440
- NLM abbreviation
- J Leukoc Biol
- ISSN
- 0741-5400
- eISSN
- 1938-3673
- Publisher
- Society for Leukocyte Biology
- Grant note
- name: Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development; DOI: 10.13039/100000002, name: U.S. National Institutes of Health, award: RO1 AI-58740; name: U.S. National Institutes of Health, Developmental Center for AIDS Research, award: P30 AI-082151-01, P01 AI-076174-01A1
- Language
- English
- Date published
- 05/2013
- Academic Unit
- Microbiology and Immunology; Infectious Diseases; Internal Medicine
- Record Identifier
- 9984094372402771
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