Abundant Tax protein expression in CD4+T cells infected with human T-cell lymphotropic virus type I (HTLV-I) is prevented by cytotoxic T lymphocytes

The role of the cellular immune response in human T-cell leukemia Virus typ e I (HTLV-I) infection is not fully understood. A persistently activated cy totoxic T lymphocyte (CTL) response to HTLV-I is found in the majority of i nfected individuals. However, it remains unclear whether this CTL response is protective or causes tissue damage. In addition, several observations pa radoxically suggest that HTLV-I is transcriptionally silent in most infecte d cells and, therefore, not detectable by virus-specific CTLs. With the use of a new flow cytometric procedure, we show here that a high proportion of naturally infected CD4+ peripheral blood mononuclear cells (PBMC) (between 10% and 80%) are capable of expressing Tax, the Immunodominant target anti gen recognized by virus-specific CTLs, Furthermore, we provide direct evide nce that autologous CD8+ T cells rapidly kill CD4+ cells naturally infected with HTLV-I and expressing Tax in vitro by a perforin-dependent mechanism, Consistent with these observations, we observed a significant negative cor relation between the frequency of Tax(11.19)-specific CD8+ T cells and the percentage of CD4+ T cells in peripheral blood of patients infected with HT LV-I, Those results are in accordance with the view that virus-specific CTL s participate in a highly efficient immune surveillance mechanism that pers istently destroys Tax-expressing HTLV-I-infected CD4+ T cells in vivo. (C) 2000 by The American Society of Hematology.