Nef-specific CD45RA+ CD8+ T cells secreting MIP-1beta but not IFN-gamma are associated with nonprogressive HIV-1 infection.
BACKGROUND
Long-term survival of HIV-1 infected individuals is usually achieved by continuous administration of combination antiretroviral therapy (ART). An exception to this scenario is represented by HIV-1 infected nonprogressors (NP) which maintain relatively high circulating CD4+ T cells without clinical symptoms for several years in the absence of ART. Several lines of evidence indicate an important role of the T-cell response in the modulation of HIV-1 infection during the acute and chronic phase of the disease.


RESULTS
We analyzed the functional and the differentiation phenotype of Nef- and Tat-specific CD8+ T cells in a cohort of HIV-1 infected NP in comparison to progressors, ART-treated seropositive individuals and individuals undergoing a single cycle of ART interruption. We observed that a distinctive feature of NP is the presence of Nef-specific CD45RA+ CD8+ T cells secreting MIP-1beta but not IFN-gamma. This population was present in 7 out of 11 NP. CD45RA+ IFN-gammaneg MIP-1beta+ CD8+ T cells were not detected in HIV-1 infected individuals under ART or withdrawing from ART and experiencing a rebounding viral replication. In addition, we detected Nef-specific CD45RA+ IFN-gammaneg MIP-1beta+ CD8+ T cells in only 1 out of 10 HIV-1 infected individuals with untreated progressive disease.


CONCLUSIONS
The novel antigen-specific CD45RA+ IFN-gammaneg MIP-1beta+ CD8+ T cell population represents a new candidate marker of long-term natural control of HIV-1 disease progression and a relevant functional T-cell subset in the evaluation of the immune responses induced by candidate HIV-1 vaccines.
Dembek
Claudia J
CJ
Institute of Virology, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Kutscher
Sarah
S
Institute of Virology, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Heltai
Silvia
S
Human Virology Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.|AIDS Immunopathogenesis Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.
Allgayer
Simone
S
Clinical Cooperation Group "Immune Monitoring", Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.|Institute of Virology, Technische Universität München, 81675 Munich, Germany.
Biswas
Priscilla
P
Laboratory of Clinical Immunology, San Raffaele Scientific Institute, 20132 Milan, Italy.
Ghezzi
Silvia
S
Viral Pathogens and Biosafety Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.
Vicenzi
Elisa
E
Viral Pathogens and Biosafety Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.
Hoffmann
Dieter
D
Institute of Virology, Technische Universität München, 81675 Munich, Germany.
Reitmeir
Peter
P
Institute of Health Economics and Health Care Management, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Tambussi
Giuseppe
G
Department of Infectious Diseases, San Raffaele Scientific Institute, 20132 Milan, Italy.
Bogner
Johannes R
JR
Department of Infectious Diseases, Medizinische Poliklinik, Ludwig Maximilians Universität, 80336 Munich, Germany.
Lusso
Paolo
P
Human Virology Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.
Stellbrink
Hans-J
HJ
Infektionsmedizinisches Centrum Hamburg ICH, 20146 Hamburg, Germany.
Santagostino
Elena
E
"A. Bianchi Bonomi" Haemophilia and Thrombosis Center, University of Milan, 20122 Milan, Italy.
Vollbrecht
Thomas
T
Department of Infectious Diseases, Medizinische Poliklinik, Ludwig Maximilians Universität, 80336 Munich, Germany.
Goebel
Frank D
FD
Department of Infectious Diseases, Medizinische Poliklinik, Ludwig Maximilians Universität, 80336 Munich, Germany.
Protzer
Ulrike
U
Institute of Virology, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.|Clinical Cooperation Group "Immune Monitoring", Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.|Institute of Virology, Technische Universität München, 81675 Munich, Germany.
Draenert
Rika
R
Department of Infectious Diseases, Medizinische Poliklinik, Ludwig Maximilians Universität, 80336 Munich, Germany.
Tinelli
Marco
M
Division of Infectious and Tropical Diseases, Hospital of Lodi, 26866 Lodi, Italy.
Poli
Guido
G
AIDS Immunopathogenesis Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.|Vita-Salute San Raffaele University, School of Medicine, 20132, Milano, Italy.
Erfle
Volker
V
Institute of Virology, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.|Clinical Cooperation Group "Immune Monitoring", Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Malnati
Mauro
M
Human Virology Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.
Cosma
Antonio
A
Institute of Virology, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.|Clinical Cooperation Group "Immune Monitoring", Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany.