Multi-clonal expansion of unique human T-lymphotropic virus type-I-infected T cells with high growth potential in response to interleukin-2 in prodromal phase of adult T cell leukemia

We established a simple IL-2-dependent colony-forming assay for T cells inf ected with human T-lymphotropic virus type-I (HTLV-I). IL-2-dependent cell lines were subsequently established by expanding individual colonies in liq uid cultures. Lymphocyte-rich fractions were prepared from 31 HTLV-I carrie rs, 12 patients with smoldering ATL, 11 chronic ATL, 12 crisis ATL and 10 a cute ATL. Primary colonies of CD4(+) p19(+) T cells were formed in all case s of carriers, smoldering and chronic ATL, and in 10 of 12 crisis cases. In contrast, no colony was formed from cells of patients with acute ATL. The rate of establishment of cell lines in HTLV-I carriers was significantly lo wer than that in patients of prodromal phase ATL. Cell lines established fr om cells of three prodromal cases were clonally identical to the parent ATL cells, while others had clonally distinct cell lines. Our results indicate d the presence of four components of HTLV-I-infected T cells: (1) normal ca rrier T cells capable of forming colonies but not cell lines; (2) pre-malig nant T cells capable of forming colonies as well as cell lines; (3) maligna nt T cells capable of forming colonies as well as cell lines; (4) fully mal ignant T cells unresponsive to IL-2. Our results suggest the presence of a multiclonal expansion of unique T cells in the prodromal phase of ATL, whic h have a high growth potential in response to IL-2. The coexistence of mult iclonality with a dominant AIL clone may be closely related to the underlyi ng pathology in HTLV-I leukemogenesis.