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.