Nef-specific CD45RA+ CD8+ T cells secreting MIP-1β but not IFN-γ are associated with nonprogressive HIV-1 infection

doi:10.1186/1742-6405-7-20

AIDS Research and Therapy

Volume 7

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Dembek CJ
Kutscher S
Heltai S
Allgayer S
Biswas P
Ghezzi S
Vicenzi E
Hoffmann D
Reitmeir P
Tambussi G
Bogner JR
Lusso P
Stellbrink HJ
Santagostino E
Vollbrecht T
Goebel FD
Protzer U
Draenert R
Tinelli M
Poli G
Erfle V
Malnati M
Cosma A

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Dembek CJ
Kutscher S
Heltai S
Allgayer S
Biswas P
Ghezzi S
Vicenzi E
Hoffmann D
Reitmeir P
Tambussi G
Bogner JR
Lusso P
Stellbrink HJ
Santagostino E
Vollbrecht T
Goebel FD
Protzer U
Draenert R
Tinelli M
Poli G
Erfle V
Malnati M
Cosma A
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Nef-specific CD45RA+ CD8+ T cells secreting MIP-1β but not IFN-γ are associated with nonprogressive HIV-1 infection

Claudia J Dembek¹ , Sarah Kutscher¹ , Silvia Heltai⁴^,5 , Simone Allgayer²^,9 , Priscilla Biswas⁷ , Silvia Ghezzi⁶ , Elisa Vicenzi⁶ , Dieter Hoffmann⁹ , Peter Reitmeir³ , Giuseppe Tambussi⁸ , Johannes R Bogner¹⁰ , Paolo Lusso⁴ , Hans-J Stellbrink¹¹ , Elena Santagostino¹² , Thomas Vollbrecht¹⁰ , Frank D Goebel¹⁰ , Ulrike Protzer¹^,2^,9 , Rika Draenert¹⁰ , Marco Tinelli¹³ , Guido Poli⁵^,14 , Volker Erfle¹^,2 , Mauro Malnati⁴^* and Antonio Cosma¹^,2^*

¹Institute of Virology, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany

²Clinical Cooperation Group "Immune Monitoring", Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany

³Institute of Health Economics and Health Care Management, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany

⁴Human Virology Unit, San Raffaele Scientific Institute, 20132 Milan, Italy

⁵AIDS Immunopathogenesis Unit, San Raffaele Scientific Institute, 20132 Milan, Italy

⁶Viral Pathogens and Biosafety Unit, San Raffaele Scientific Institute, 20132 Milan, Italy

⁷Laboratory of Clinical Immunology, San Raffaele Scientific Institute, 20132 Milan, Italy

⁸Department of Infectious Diseases, San Raffaele Scientific Institute, 20132 Milan, Italy

⁹Institute of Virology, Technische Universität München, 81675 Munich, Germany

¹⁰Department of Infectious Diseases, Medizinische Poliklinik, Ludwig Maximilians Universität, 80336 Munich, Germany

¹¹Infektionsmedizinisches Centrum Hamburg ICH, 20146 Hamburg, Germany

¹²"A. Bianchi Bonomi" Haemophilia and Thrombosis Center, University of Milan, 20122 Milan, Italy

¹³Division of Infectious and Tropical Diseases, Hospital of Lodi, 26866 Lodi, Italy

¹⁴Vita-Salute San Raffaele University, School of Medicine, 20132, Milano, Italy

author email corresponding author email* Contributed equally

AIDS Research and Therapy 2010, 7:20doi:10.1186/1742-6405-7-20


Published:	2 July 2010

Abstract

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-gamma^negMIP-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-gamma^negMIP-1beta+ CD8+ T cells in only 1 out of 10 HIV-1 infected individuals with untreated progressive disease.

Conclusion

The novel antigen-specific CD45RA+ IFN-gamma^negMIP-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.