Thymosin α 1 potentiates the release by CD8⁺ cells of soluble factors able to inhibit HIV-1 and human T lymphotropic virus 1 infection in vitro

Abstract

Background: Thymosin α-1 (Tα1) exploits a specific action on lymphoid cells and is able to induce in peripheral blood mononuclear cells (PBMCs) a strong transcriptional response. CD8 antiviral factor activity plays a role in the control or prevention of HIV-1 infection by a non-cytolytic mechanism. The ability of Tα1 to modulate the release of antiretroviral soluble factors by CD8⁺ cells was investigated.

Methods: Supernatants from lipopolysaccharide (LPS) stimulated CD8⁺-isolated cells treated with Tα1 were screened on in vitro infection of human monocyte-derived macrophages (MDMs) and PBMCs with HIV-1, and of PBMCs with human T lymphotropic virus 1 (HTLV-1). In CD8⁺ cells, as well as in PBMCs of healthy donors as from HIV⁺ individuals, a microarray analysis to assess the transcriptional response after treatment was performed.

Results: Tα1 potentiates the release, in LPS-stimulated CD8⁺ cells, of soluble factors able to inhibit both in vitro HIV-1 infection of MDMs and PBMCs and in vitro HTLV-1 infection of PBMCs. A distinctive transcriptional profile was induced by Tα1 in PBMCs from HIV⁺ donors.

Conclusions: These findings suggest that Tα1 would represent a re-evaluated approach to antiretroviral therapy in combination with innovative treatments and with vaccine administration.

Keywords:

• CD8 antiviral factor
• chemokines
• HIV-1
• human T lymphotropic virus 1
• immunotherapy
• Thymosin α 1

Acknowledgments

We wish to thank Martino Tony Miele for his technical assistance.

Declaration of interest

This paper is part of a supplemental issue, sponsored by SciClone. Funding was received from the Italian Ministry of University and Research (Research Projects of National Interest), grant no. 2007KLCKP8_003, grant no. 2010NZ2XRJ_005, grant no. 2010PHT9NF_001; the Istituto Superiore di Sanità, grant no. 30F/32; and the University of Rome “Tor Vergata”, grant no. 2009-RSA0418. EG is a Thymosin patent holder. The other authors declare no conflict of interest. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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