Differential modulation of IL-4, IL-10, IL-17, and IFN-γ production mediated by IgG from Human T-lymphotropic virus-1 (HTLV-1) infected patients on healthy peripheral T (CD4+, CD8+, and γδ) and B cells

Abstract

Human T-lymphotropic virus 1 (HTLV-1) infected individuals remain as asymptomatic carriers (ACs) or can develop the chronic neurological disorder HTLV-1-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP) or the adult T-cell leukemia/lymphoma (ATLL), and the immunological mechanisms involved in this pathologies need to be elucidated. Recently, it has been demonstrated that induced or naturally developed IgG repertoires obtained from different groups of donors, grouped by immune status, can modulate human T and B cell functions. Here we aimed to evaluate if the IgG obtained from HTLV-1-infected ACs, HAM/TSP, and ATLL patients can differentially modulate the production of cytokines by human T and B cells. With this purpose, we cultured PBMCs with IgG purified from ACs, HAM/TSP, or ATLL donors and evaluated the frequency and intracellular cytokine production by flow cytometry. Our results indicate that IgG from HAM/TSP patients could induce an augment of IL-17-producing CD4+ T cells, reduce the frequency of IL-4-producing CD4+ T cells, increase IFN-γ-producing CD8+ T cells, and reduce IL-4-producing CD8+ T cells. IgG from ATLL could reduce the frequency of IL-4-producing CD4+ T cells, similarly to IgG from HAM/TSP /TSP, and could reduce the frequency of IFN-γ-producing γδT cells without influence on IL-17- and IL4-producing γδT and could reduce the frequency of IL-10- producing B cells. Finally, IgG from both HAM/TSP and ATLL patients could reduce the frequency of IFN-γ producing B cells. In conclusion, these results suggest that these preparations are active, partly overlapping in their effects, and able to elicit distinct effects on target populations.

Interferon gamma as a trigger of chronic viral infections and inflammatory dermatoses

“…Помимо этого, N.R. Machado et al показывают, что IgG у пациентов, инфицированных HTLV-1, могут способствовать увеличению CD4 + Т-клеток, продуцирующих IL-17, и снижать количество CD4 + Т-клеток, продуцирующих IL-4, при этом повышается количество CD8 + Т-клеток, продуцирующих IFN-γ, и снижается -IL-4-продуцирующих CD8 + Т-клеток [54].…”

IgG from Dermatophagoides pteronyssinus (Der p)-atopic individuals modulates non-atopic thymic B cell phenotype (alfa-4/beta-7) and cytokine production (IFN-γ, IL-9, and IL-10) with direct membrane interaction

“…Recently, the "hooks without bait" immunological hypothesis proposed that polyclonal IgG repertoires from different donor groups may play essential roles in modulating the function of thymic and peripheral T and B cells 16 . In this context, polyclonal IgG from individuals with allergies, atopic dermatitis, HIV infection, and HTLV infection has demonstrated in vitro modulatory effects on various thymic and peripheral lymphocytes, including T cells, B cells, γδT cells, iNKT cells, and innate-like cells (ILC) in both humans and mice 17 – 25 . These effects have the potential to modulate the pathophysiology of these diseases.…”