IL-10 produced by CD4+ and CD8+ T cells emerge as a putative immunoregulatory mechanism to counterbalance the monocyte-derived TNF-α and guarantee asymptomatic clinical status during chronic HTLV-I infection

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Abstract
Although it is believed widely that distinct patterns of the host immune response are associated with the outcome of chronic human T cell lymphotropic virus type 1 (HTLV-I) infection toward asymptomatic or symptomatic neurodegenerative myelopathy (HAM/TSP), the exact mechanism underlying these immunological events still remains unknown. In this study, we have evaluated the cytokine pattern [interleukin (IL)-12, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, IL-4 and IL-10] of innate and adaptive immunity cells present at the peripheral blood from non-infected (NI) and HTLV-I infected individuals [asymptomatic (AS), oligosymptomatic (OL) and HAM/TSP-HT], following in vitro short-term incubation in the absence/presence of phorbol myristate acetate (PMA) pan-leucocyte stimulation. In the absence of PMA stimulation, our data demonstrate that despite the overall immunological profile of AS mimicry that observed for NI, the high frequency of IL-12+ neutrophils and TNF-α+ monocytes are also a hallmark of this group of individuals. However, the outstanding positive correlation between the high frequency of TNF-α+ monocytes and high levels CD4+ IL-10+ and CD8+ IL-10+ T cells suggests the establishment of immunoregulatory mechanisms that guarantee their asymptomatic clinical status. On the other hand, OL and HT did not present any association between the high frequency and TNF-α+ neutrophils and monocytes and this immunoregulatory profile at their adaptive immunity cells. Upon PMA-index analysis, high levels of type 1 CD4+ T cells, as well as higher IFN-γ/IL-10 and TNF-α/IL-10 ratios, were observed in HT, and re-emphasize the role of Th1-cytokines from CD4+ cells to HTLV-I immunity and disease. Moreover, increasing frequency of CD8+ IFN-γ+ and CD8+ TNF-α+ cells were observed in the HT, which corroborates the marked inflammatory profile underlying this pathological condition and the role of CD8+ T cells in the pathogenesis of HAM/TSP.