Accumulation of DC-SIGN+CD40+ dendritic cells with reduced CD80 and CD86 expression in lymphoid tissue during acute HIV-1 infection.
BACKGROUND
Dendritic cells (DC) are target cells for HIV-1 and play a key role in antigen presentation and activation of T cells.


OBJECTIVE
To characterize interdigitating DC in lymphoid tissue (LT) with regard to maturation, expression of cytokines and co-stimulatory molecules in HIV-1-positive patients.


METHODS
DC were characterized by immunohistochemistry and in situ imaging in LT from patients with acute HIV-1 infection (aHI), antiretroviral treated patients, long-term non-progressors/slow progressors with HIV-1 infection (LTNP/SLP), patients with AIDS, HIV-1-negative controls and patients with acute Epstein-Barr virus (EBV) infection.


RESULTS
A significant increase of interdigitating DC expressing CD1a, S-100b, CD83 and DC-SIGN was found in LT from patients with aHI (P < 0.02). The co-stimulatory molecules CD80 and CD86 were, however, only partially upregulated and the complete parafollicular network found in acute EBV infection was not generated, despite increased expression of interleukins 1alpha, 1beta, 12; interleukin 1alpha receptor antagonist; interferon alpha; and CD40 expression. LTNP/SLP and treated aviremic subjects had increased frequency of interdigitating DC, albeit lower than in aHI, and low expression of CD80 and CD86. In contrast, patients with AIDS had fewer DC and reduced cytokine expression in LT.


CONCLUSIONS
In the early phase of HIV-1 infection, there was a migration of DC to LT comparable to that found in acute EBV infection. The infiltration of DC in LT in acute EBV infection was accompanied by upregulation of CD80 and CD86 expression, which did not occur in aHI. This co-stimulatory defect in aHI may have an impact on the development of HIV-1-specific T cell immunity.
Loré
Karin
K
Division of Clinical Virology, Department of Microbiology, Pathology and Immunology, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden. klore@mail.nih.gov
Sönnerborg
Anders
A
Broström
Christina
C
Goh
Li-Ean
LE
Perrin
Luc
L
McDade
Hugh
H
Stellbrink
Hans-Jürgen
HJ
Gazzard
Brian
B
Weber
Rainer
R
Napolitano
Laura A
LA
van Kooyk
Yvette
Y
Andersson
Jan
J
D000208:Acute Disease; D015703:Antigens, CD / Q000096:biosynthesis*; D018122:B7-1 Antigen / Q000096:biosynthesis*; D051940:B7-2 Antigen; D015415:Biomarkers; D019013:CD40 Antigens / Q000276:immunology*; D016827:CD8 Antigens / Q000096:biosynthesis; D015815:Cell Adhesion Molecules; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D037102:Lectins / Q000276:immunology*; D037181:Lectins, C-Type; D008221:Lymphoid Tissue / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D011956:Receptors, Cell Surface / Q000276:immunology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D015415:Biomarkers; D019013:CD40 Antigens; D016827:CD8 Antigens; D015815:Cell Adhesion Molecules; D016207:Cytokines; D037102:Lectins; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin