Immune modulation via dendritic cells by the effect of Thymosin-alpha-1 on immune synapse in HCMV infection

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Thymosin-alpha-1 (Tα1) is a thymus-derived peptide hormone with known immunomodulatory properties.
• Human cytomegalovirus (HCMV) infection poses significant risks, especially to immunocompromised individuals.
• Understanding Tα1's effects on immune cells during HCMV infection is crucial for developing novel therapeutic strategies.

Purpose of the Study:

• To investigate the in vitro immunomodulatory effects of Tα1 on dendritic cells (DCs) and T-lymphocytes (TLs) during HCMV infection.
• To assess how Tα1 influences DC maturation markers and cytokine production.
• To evaluate Tα1's impact on T-lymphocyte responses, including cytokine production and polyfunctionality, in the context of HCMV.

Main Methods:

• Dendritic cells (DCs) were isolated from peripheral blood mononuclear cells (PBMCs) and treated with Tα1.
• DC immunophenotyping was performed using multiparametric flow cytometry for markers like CD40, CD80, TIM-3, and PDL-1, along with intracellular TNFα.
• Autologous CD4+ and CD8+ T-lymphocytes (TLs) were co-cultured with Tα1-treated DCs in the presence or absence of HCMV, followed by assessment of cytokine production and surface marker expression.

Main Results:

• Tα1 treatment increased DC expression of CD40, CD80, TIM-3, and intracellular TNFα, while decreasing PDL-1, particularly on plasmacytoid DCs (pDCs).
• Tα1 modulated TNFα, IFNγ, and IL-2 production in both CD4+ and CD8+ TLs, upregulating CD40/CD40-L and downregulating PDL-1/PD-1 expression.
• The study demonstrated enhanced T-lymphocyte polyfunctionality, especially in CD8+ TLs, following Tα1 treatment.

Conclusions:

• Tα1 enhances the antigen-presenting capacity of dendritic cells.
• Tα1 treatment improves T-lymphocyte responses to HCMV infection.
• Tα1 shows potential as an adjuvant in therapeutic cell therapy for immunocompromised patients.