Loss of DNAM-1 contributes to CD8+ T-cell exhaustion in chronic HIV-1 infection.
The hallmark of chronic viral infections is a progressive exhaustion of antigen-specific CD8(+) T cells that leads to persisting viral replication. It is generally believed that exhaustion is a consequence of the accumulation of multiple inhibitory receptors on CD8(+) T cells that makes them dysfunctional. Here, we show that during human chronic HIV-1 infection, a CD8(+) T-cell positive costimulatory pathway mediated by DNAX-activating molecule-1 is also disrupted. Thus, DNAX-activating molecule-1 downregulation on CD8(+) T cells aggravates the impairment of CTL effector function in chronic HIV-1 infection.
Cella
Marina
M
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Presti
Rachel
R
Vermi
William
W
Lavender
Kerry
K
Turnbull
Emma
E
Ochsenbauer-Jambor
Christina
C
Kappes
John C
JC
Ferrari
Guido
G
Kessels
Lisa
L
Williams
Ian
I
McMichael
Andrew J
AJ
Haynes
Barton F
BF
Borrow
Persephone
P
Colonna
Marco
M
D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D015536:Down-Regulation; D006023:Glycoproteins / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D051379:Mice; D010446:Peptide Fragments / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor; D011991:Receptors, Virus / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity; D019562:Viral Load; D014764:Viral Proteins / Q000276:immunology; D014779:Virus Replication; D000098862:T Lineage-Specific Activation Antigen 1
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000956:Antigens, Viral; D051017:Apoptosis Regulatory Proteins; D000098862:T Lineage-Specific Activation Antigen 1; D006023:Glycoproteins; C105992:PDCD1 protein, human; D010446:Peptide Fragments; D061026:Programmed Cell Death 1 Receptor; D011991:Receptors, Virus; D014764:Viral Proteins; C094244:glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus; C066100:poliovirus receptor