Reduced blood CD123+ (lymphoid) and CD11c+ (myeloid) dendritic cell numbers in primary HIV-1 infection.
Successful immunologic control of HIV infection is achieved only in rare individuals. Dendritic cells (DCs) are required for specific antigen presentation to naive T lymphocytes and for antiviral, type I interferon secretion. Two major blood DC populations are found: CD11c+ (myeloid) DCs, which secrete IL-12, and CD123+ (IL-3-receptor+) DCs (lymphoid), which secrete type I interferons in response to viral stimuli. The authors have previously found a decreased proportion of blood CD11c+ DCs in chronic HIV+ patients. In this study, 26 to 57 days after infection and before treatment, CD123+ and CD11c+ DC numbers were dramatically reduced in 13 HIV+ patients compared with 13 controls (P =.0002 and P =.001, respectively). After 6 to 12 months of highly active antiretroviral therapy, DC subpopulation average numbers remained low, but CD123+ DC numbers increased again in 5 of 13 patients. A strong correlation was found between this increase and CD4 T-cell count increase (P =.0009) and plasma viral load decrease (P =.009). Reduced DC numbers may participate in the functional impairment of HIV-specific CD4+ T cells and be responsible for the low type I interferon responsiveness already known in HIV infection. The restoration of DC numbers may be predictive of immune restoration and may be a goal for immunotherapy to enhance viral control in a larger proportion of patients.
Pacanowski
J
J
Unité INSERM 445, Immunologie des pathologies infectieuses et tumorales, Département d'Immunologie, Institut Cochin de Génétique Moléculaire and Laboratoire de Virologie, Hôpital St-Vincent de Paul, Paris, France.
Kahi
S
S
Baillet
M
M
Lebon
P
P
Deveau
C
C
Goujard
C
C
Meyer
L
L
Oksenhendler
E
E
Sinet
M
M
Hosmalin
A
A
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D001772:Blood Cell Count; D018791:CD4 Lymphocyte Count; D003713:Dendritic Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D015497:HIV-1; D006801:Humans; D016167:Integrin alphaXbeta2 / Q000032:analysis*; D016898:Interferon-alpha / Q000097:blood / Q000172:deficiency / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D053650:Interleukin-3 Receptor alpha Subunit; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000378:metabolism / Q000473:pathology; D012367:RNA, Viral / Q000097:blood; D016185:Receptors, Interleukin-3 / Q000032:analysis*; D019562:Viral Load
C115022:IL3RA protein, human; D016167:Integrin alphaXbeta2; D016898:Interferon-alpha; D053650:Interleukin-3 Receptor alpha Subunit; D012367:RNA, Viral; D016185:Receptors, Interleukin-3; D018664:Interleukin-12