Immunity and Genetic Resistance to Tropical Theileriosis
Theileria annulata is a tick-borne protozoan parasite of cattle and
the causative agent of tropical theileriosis, or East Coast Fever. This
disease is a serious constraint to the improvement of cattle in endemic areas
of Africa, as European cattle imported to improve milk and meat yields are
extremely susceptible to the disease. The disease can be controlled by a
vaccine containing live parasite, but data about its impact on endemic areas
was previously sketchy. A programme of research, funded by the European Union
Science and Technology for Development (STD) programme, examined two areas
which are essential in combatting this disease problem:
1.- The mechanisms employed by the parasite to avoid immune detection
leading to disease.
2.- The first major epidemiological surgery in an endemic area
(Morocco).
1.- In experimentally treated animals, where the parasite was killed by drug
treatment, it had been shown that T cells could be generated by the host to
reject the parasite.
Continuing work from an earlier STD funded programme, this work showed that T.
annulata is in a unique position to influence the generation of such T cell
responses, as it infects the antigen presenting cells (APC) which are
responsible for the induction of T cell responses.
When T cells were stimulated by T. annulata infected APC, it was found
that although the T cells were induced to activate and grow, that they did not
acquire any specificity for the parasite. This was true of both CD8+ T cells,
which directly kill infected cells and CD4+ T cells which are responsible for
the production of soluble factors to "help" CD8+ acquire a "killer" phenotype.
The failure to produce protective immunity during. T. annulata infection of
susceptible animals is therefore at least partly due to alteration of normal
immune response pathways by the parasite.
2.- The first major epidemiological survey of theileriosis was carried out in
Morocco, giving invaluable data on disease prevalence. Approaching 100% of
cattle in endemic areas were infected, although disease was principally
confined to European cattle. As the majority of animals were infected, there
was no possibility that the vaccine would induce new "carrier" cattle to the
population. This information was used in designing and carrying out a large
scale tissue culture vaccination programme, using a dose 100 times lower than
attempted in other countries. The trial was extremely successful and the low
dose significantly reduced the cost and increased the safety of the vaccine.
The findings from both areas of the project have provided the basis
for large advances in the control of tropical theileriosis. Vaccination in
Morocco has now been extended to very large numbers of cattle, and vaccine
production is currently being commercialised. The research team has
subsequently shown that aberrant T cell responses are the critical event in
the induction of disease, leading to sequential immune response failure.
For further information contact the project leader, Dr. Roger C.
Spooner, Roslin Institute, Edinbrugh EH25 9PS.