Modulation of T Cell Responses in HTLV-1 Carriers and in Patients with Myelopathy Associated with HTLV-1

Abstract

Objective: Human T lymphotropic virus-type 1 (HTLV-1) activates the immune system leading to a persistent and exacerbated T-cell response with increased production of IFN-γ and TNF-α. Overproduction of pro-inflammatory cytokines is correlated with the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), although some HTLV-1 carriers also show high levels of these cytokines. In this study, the ability of regulatory cytokines and cytokine antagonists to inhibit spontaneous IFN-γ production was investigated. Method: IFN-γ levels were measured by ELISA before and after addition of cytokines or anti-cytokines. Results: Addition of IL-10 significantly reduced spontaneous IFN-γ synthesis in cell cultures from HTLV-1 carriers, while no differences were observed in HAM/TSP patients. There was also a tendency to decreased IFN-γ levels in cell cultures from HTLV-1 carriers with exogenous addition of TGF-β. In paired analysis, neutralization of IL-2 significantly decreased IFN-γ production in HTLV-1 carriers but not in HAM/TSP patients. Neutralization of IL-15 was less effective than neutralization of IL-2 in modulating IFN-γ production. In HTLV-1 carriers, anti-IL-2 and simultaneous addition of anti-IL-2 and anti-IL-15 decreased IFN-γ synthesis by 46 and 64%, respectively, whereas in patients with HAM/TSP simultaneous neutralization of both anti-cytokines only decrease IFN-γ levels by 27%. Conclusions: Although a large proportion of HTLV-1 carriers produced high levels of pro-inflammatory cytokines similar to those observed in HAM/TSP patients, immune response can be downregulated by cytokines or cytokine antagonists in most HTLV-1 carriers. This modulation can be an important step in the prevention of tissue damage and progression from the HTLV-1 carrier state to HAM/TSP.

Infective dermatitis has similar immunological features to human T lymphotropic virus-type 1-associated myelopathy/tropical spastic paraparesis

“…We have previously shown that IL-10, anti-IL-2 and anti-IL-15 down-modulate IFN-g production in HTLV-1 carriers but do not suppress IFN-g synthesis in HAM/TSP [25]. In this study we evaluated whether the exogenous addition of IL-10 and neutralization of IL-2 and IL-15 was able to downmodulate IFN-g synthesis in cell cultures.…”

“…We have previously shown that while PBMCs from HTLV-1 carriers can be modulated when IL-10 and anti-IL-2 are added in vitro, cells from HAM/TSP patients exhibit poor modulation of the immune response [25]. To evaluate the ability of IL-10 to decrease the spontaneous IFN-g production observed in HTLV-1-infected patients, PBMCs of IDH patients and HTLV-1 carriers were cultured in the presence of IL-10.…”

<b><i>Schistosoma</i></b> Antigens Downmodulate the in vitro Inflammatory Response in Individuals Infected with Human T Cell Lymphotropic Virus Type 1

“…Recently, the inability of the recombinant human IL-10 in downmodulating IFN-γ production in vitro in HAM/TSP individuals was described [22]. However, the low ratio of IFN-γ/IL-10 induced by some Schistosoma spp.…”

Clinical and immunological features of patients with atopy and concomitant HTLV-1 infection

“…Additionally, HTLV-1 infection may influence the immune response to other pathogens, increasing susceptibility and modifying the clinical manifestation of strongyloidiasis (4,5), tuberculosis (6,7), schistosomiasis (8), and scabies (9). The pathology related to HTLV-1 infection is associated with an exaggerated and inappropriately modulated immune response, and a high proviral load (10). The mechanisms related to the ability of HTLV-1 to increase susceptibility or influence the clinical course of other diseases are not fully understood.…”