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

Background: Thymosin a-1 (Ta1) 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 Ta1 to modulate the release of antiretroviral soluble factors by CD8+ cellswas investigated. Methods: Supernatants from lipopolysaccharide (LPS) stimulated CD8+- isolated cells were treated with Ta1 and 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: Ta1 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 Ta1 in PBMCs from HIV+ donors. Conclusions: These findings suggest that Ta1 would represent a re-evaluated approach to antiretroviral therapy in combination with innovative treatments and with vaccine administration.