THE CYTOTOXIC T-LYMPHOCYTE RESPONSE TO HTLV-I - THE MAIN DETERMINANT OF DISEASE

There is a powerful, chronically activated cytotoxic T-lymphocyte (CTL ) response to the Tax protein of human T-cell leukaemia virus type I ( HTLV-I) in most people infected with the virus. The CTL select variant sequences of Tax which escape immune recognition and interfere with r ecognition of the wild-type protein. This positive selection process i s more efficient in healthy HTLV-I carriers than in patients with trop ical spastic paraparesis, an inflammatory neurological disease associa ted with HTLV-I. The mean virus load is more than 10-fold greater in p atients with this neurological disease than in healthy carriers of HTL V-I. We conclude that anti-Tax CTL play an important part in limiting the rate of replication of HTLV-I. We suggest that the outcome of infe ction with HTLV-I is primarily determined by the CTL response of the i ndividual: low CTL responders to HTLV-I develop a high virus load, res ulting in widespread chronic activation of T cells. The activated T ce lls then invade the tissues and cause bystander tissue damage, probabl y by releasing cytokines and other soluble substances. An efficient CT L response to HTLV-I limits the equilibrium virus load, and so reduces the chance of developing inflammatory disease.