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

Claudia J. Dembek, Sarah Kutscher, Silvia Heltai, Simone Allgayer, Priscilla Biswas, Silvia Ghezzi, Elisa Vicenzi, Dieter Hoffmann, Peter Reitmeir, Giuseppe Tambussi, Johannes R. Bogner, Paolo Lusso, Hans J. Stellbrink, Elena Santagostino, Thomas Vollbrecht, Frank D. Goebel, Ulrike Protzer, Rika Draenert, Marco Tinelli, Guido PoliVolker Erfle, Mauro Malnati, Antonio Cosma

Research output: Contribution to journalArticlepeer-review

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-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.Conclusion: 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.

Original languageEnglish
Article number20
JournalAIDS Research and Therapy
Volume7
DOIs
Publication statusPublished - Jul 2 2010

ASJC Scopus subject areas

  • Virology
  • Molecular Medicine
  • Pharmacology (medical)

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