Cytotoxic T cell response and expression of the target antigen in HTLV-I infection.

The cytotoxic T cell response of peripheral blood mononuclear cells (PBMC) to in vitro stimulation with human T cell leukemia virus type I (HTLV-I) was compared among HTLV-I-infected individuals with various clinical conditions. Induction of HTLV-I-specific cytotoxic T lymphocytes (CTL) was observed in 57% of asymptomatic HTLV-I carriers, 86% of patients with HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) or other HTLV-I-related inflammatory diseases, and 18% of adult T cell leukemia (ATL) patients. HTLV-I p40tax, one of the major CTL target antigens, has an epitope strongly associated with HLA-A2. HTLV-I p40tax-specific CTL were frequently induced from HLA-A2-positive donors with HTLV-I-related inflammatory diseases regardless of neurological symptoms, but not from all the HLA-A2-positive HTLV-I-infected individuals tested. Leukemic cells of an ATL patient with HLA-A2, whose PBMC did not show an HTLV-I-specific CTL response, could be lyzed by p40tax-specific CTL derived from an HAM/TSP patient. This indicates that i) the presence of a certain HLA presenting CTL epitopes is not the sole determinant of the individual CTL response to HTLV-I, ii) HTLV-I-specific CTL act as potential effectors of anti-tumor surveillance in vivo. The role of HTLV-I-specific CTL, however, may be limited by another in vivo mechanism suppressing the expression of HTLV-I antigens. This suppression, presumably mediated by a plasma factor and commonly observed in HTLV-I-infected individuals, could be one reason for the persistence of HTLV-I-infection.