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Impaired Tax‐specific T‐cell responses with insufficient control of HTLV‐1 in a subgroup of individuals at asymptomatic and smoldering stages

Human T‐cell leukemia virus type‐1 (HTLV‐1)‐specific T‐cell immunity, a potential antitumor surveillance system in vivo, is impaired in adult T‐cell leukemia (ATL). In this study, we aimed to clarify whether the T‐cell insufficiency in ATL is present before the disease onset or occurs as a consequence of the disease. We investigated T‐cell responses against Tax protein in peripheral blood mononuclear cells (PBMCs) from individuals at earlier stages of HTLV‐1‐infection, including 21 asymptomatic HTLV‐1 carriers (ACs) and four patients with smoldering‐type ATL (sATL), whose peripheral lymphocyte count was in normal range. About 30% of samples tested showed clear Tax‐specific interferon (IFN)‐γ producing responses. Proviral loads in this group were significantly lower than those in the other less‐specific response group. The latter group was further divided to two subgroups with or without emergence of Tax‐specific responses following depletion of CC chemokine receptor 4 (CCR4)+ cells that contained HTLV‐1‐infected cells. In the PBMCs with Tax‐specific responses, CD8+ cells efficiently suppressed HTLV‐1 p19 production in culture. The remaining group without the emergence of Tax‐specific response after CCR4+ cell‐depletion included at least two sATL and one AC samples, which spontaneously produced HTLV‐1 p19 in culture, where tetramer‐binding, Tax‐specific cytotoxic T‐lymphocytes were either undetectable or unresponsive. Our results indicated that HTLV‐1‐specific T‐cell responsiveness widely differed among HTLV‐1 carriers, and that impairment of HTLV‐1‐specific T‐cell responses was observed not only in advanced ATL patients but also in a subpopulation at earlier stages, which was associated with insufficient control of HTLV‐1. (Cancer Sci 2009; 100: 481–489)