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

Expert Opin Biol Ther. 2015:15 Suppl 1:S83-100. doi: 10.1517/14712598.2015.1021677. Epub 2015 Jun 22.

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; HIV-1; Thymosin α 1; chemokines; human T lymphotropic virus 1; immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • CD8 Antigens / immunology
  • CD8 Antigens / metabolism*
  • Deltaretrovirus Infections / drug therapy
  • Deltaretrovirus Infections / immunology
  • Deltaretrovirus Infections / metabolism
  • Drug Synergism
  • HIV Infections / immunology
  • HIV-1 / drug effects*
  • HIV-1 / immunology
  • Human T-lymphotropic virus 1 / drug effects*
  • Human T-lymphotropic virus 1 / immunology
  • Human T-lymphotropic virus 1 / metabolism
  • Humans
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Thymalfasin
  • Thymosin / analogs & derivatives*
  • Thymosin / pharmacology
  • Thymosin / therapeutic use

Substances

  • Antiviral Agents
  • CD8 Antigens
  • Thymosin
  • Thymalfasin