Functional analysis of Foxp3 and CTLA-4 expressing HTLV-1-infected cells in a rat model.

Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia (ATL). Some ATL cells express Foxp3, which is known as regulatory T cell (Treg cell) specific transcription factor. It is suggested that Treg cell like suppressive activity of Foxp3 expressing ATL cells is associated to ATL development and related immunodeficiency. To develop an HTLV-1 model system that enables to investigate the association of Treg function in ATL progression, we examined the expression of Foxp3 and CTLA-4, Treg cell-associated factor, in established HTLV-1-infected rat cell lines and their regulatory function. We found the expression of Foxp3 in 10 of 22 and CTLA-4 in 10 of 19 HTLV-1-infected rat cell lines. Moreover, some of the Foxp3 and/or CTLA-4 expressing cell lines suppressed proliferation of naïve T cells that were stimulated with anti-CD3 antibody. Particularly all Foxp3(+) CTLA-4(+) cells showed the suppressive activity. Our data suggest the usefulness of our rat model systems for further analysis of the role of Treg cell-associated factors on the development of ATL and related immunodeficiency in vivo.