Autoproliferative and self-reactive T-cell lines from patients with HTLV-I-associated myelopathy

In two patients with human T lymphotropic virus type 1 (HTLV-I)-associated myelopathy (HAM) and a non-HAM HTLV-I carrier, T-cell lines were generated and characterized from cerebrospinal fluid (CSF) lymphocytes and peripheral blood lymphocytes (PBL). In total, 62 T-cell lines were established using direct plating technique for expanding human T lymphocytes. Sixty three percent of the T-cell lines were CD4+, CDw29+ and HTLV-I gag+. CD8+T-cell lines were also established and they were gag-. Proliferation in the absence of additional antigens and exogenous interleukin 2 ("autoproliferation") was observed in 61% of the T-cell lines and significantly correlated with HTLV-I antigen (gag) expression. In addition, some T-cell lines from HAM patients exhibited proliferative response to self PBL, and the magnitude of their responses was diverse according to the phenotypes of stimulating cells. Therefore, the spontaneous lymphoproliferation observed in patients with HAM is generated by three components; HTLV-I-infected T cells and T cells reactive against HTLV-I and against self antigens. Since most gag+ T-cell lines produced lymphotoxin (LT)/tumor necrosis factor alpha (TNF alpha), it is suggested that those T cells are playing important roles in the pathogenesis of HAM.