ATLL is an aggressive
malignancy of T cells that affects about 5% of individuals infected with HTLV-1. The precise mechanism of
oncogenesis is not known, but there is evidence that two regulatory
viral proteins, Tax and HBZ, are involved. A high set point proviral load is associated with development of
ATLL or a chronic inflammatory condition, HAM/TSP. Several lines of evidence, including HLA class 1 association studies and in vitro killing assays, indicate that cytotoxic T lymphocytes are instrumental in determining this proviral load set point. Prior studies have focused chiefly on the CTL response to the immunodominant
Tax protein: efficient lysis of Tax-expressing cells inversely correlates with proviral load in nonmalignant
infection. However, a recent study showed that strong binding of
peptides from HBZ, but not Tax, to HLA class 1 molecules was associated with a low proviral load and a reduced risk of developing HAM/TSP, indicating an important role for HBZ-specific CTL in determining
infection outcome. In comparison with nonmalignant
infection, HTLV-1-specific CTLs in
ATLL patients are reduced in frequency and functionally deficient. Here we discuss the nature of protective CTL responses in nonmalignant HTLV-1
infection and explore the potential of CTLs to protect against
ATLL.