Involvement of IL-2/IL-2R system activation by parasite antigen in polyclonal expansion of CD4+25+ HTLV-1-infected T-cells in human carriers of both HTLV-1 and S. stercoralis

Abstract

The intermediate state of HTLV-1 infection, often found in individuals dually infected with Strongyloides stercoralis (S. stercoralis) and HTLV-1, is assumed to be a preleukemic state of adult T-cell leukemia (ATL). To investigate the e ects of S. stercoralis superinfection on the natural history of HTLV-1 infection, we characterized peripheral blood samples of these individuals in Okinawa, Japan, an endemic area for both HTLV-1 and S. stercoralis and we studied e ects of the parasite antigen on T-cells. The dually infected individuals showed a signi®cantly higher provirus load and an increase in CD4 + 25 + T cell population, with a signi®cant, positive correlation. This increase was attributable to polyclonal expansion of HTLV-1-infected cells, as demonstrated by inverse-long PCR analysis of the integration sites. S. stercoralis antigen activated the IL-2 promoter in reporter gene assays, induced production of IL-2 by PBMC in vitro, and supported growth of IL-2 dependent cell lines immortalized by HTLV-1 infection or the transduction of Tax. Taken collectively, these results indicate that S. stercoralis infection induces polyclonal expansion of HTLV-1-infected cells by activating the IL-2/IL-2R system in dually infected carriers, an event which may be a precipitating factor for ATL and in¯ammatory diseases.

Effect of treatment of Strongyloides infection on HTLV‐1 expression in a patient with adult T‐cell leukemia

“…Alternatively, a Strongyloides antigen has been postulated to induce a potent polyclonal T-cell mitogenic response, and reactivation of HTLV-1 expression [1,20]. Although the patient's ALC and viral DNA load did not decline after ivermectin treatment, the dramatic drop in viral RNA after treatment suggests that Strongyloides was a potent stimulus for virus expression, presumably through T-cell activation.…”

Oncolytic activity of vesicular stomatitis virus in primary adult T-cell leukemia

“…Previous studies have demonstrated that activation of the IL-2/IL-2R loop during the acute phase of HTLV-1 infection contributes to the activation and proliferation of HTLV-1-infected CD4 þ CD25 þ subset of ATL cells (Maruyama et al, 1987;Satoh et al, 2002). Thus, we next examined the effect of cell activation on VSV permissiveness and cytolytic activity.…”

Complicated and fatal Strongyloides infection in Canadians: risk factors, diagnosis and management

“…HTLV-1 is a retrovirus associated with adult T-cell leukemia and HTLV-1-associated myelopathy, 37 with adult T-cell leukemia developing in 3%-5% of HTLV-1 carriers after a long period of latency. 38 This latent or preleukemic phase is reported to be up to 30 years shorter in HTLV-1 carriers who are coinfected with Strongyloides than in other HTLV-1-infected people.…”