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ß T Cell Response to Toxoplasma gondii in Previously Unexposed Individuals1



,§
*
Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, OH 45267;
Research Institute Palo Alto Medical Foundation, Palo Alto, CA 94301;
DNAX Research Institute of Molecular and Cellular Biology, Inc., Palo Alto, CA 94304; and
§
Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, CA 94305
The mechanisms by which T cells from previously unexposed hosts
respond in vitro to certain intracellular pathogens remain to be fully
understood. We report and characterize the in vitro reactivity to
Toxoplasma gondii of human
ß T cells from T.
gondii-seronegative individuals. Resting
ß T cells from
these individuals proliferated in response to PBMC infected with
T. gondii or pulsed with T. gondii lysate Ags.
This was accompanied by an increase in the percentage of
CD4+
ß T cells. Purified CD4+
ß T
cells but not CD8+
ß T cells proliferated in response
to these T. gondii preparations. Both CD4+
ß T cells with naive (CD45RA+) and memory
(CD45RO+) phenotypes from adults as well as
ß T cells
from T. gondii-seronegative newborns proliferated after
incubation with T. gondii. This
ß T cell response to
the parasite was inhibited by anti-HLA-DR mAb and to a lesser
degree by anti-HLA-DQ mAb. Use of paraformaldehyde-fixed PBMC
completely abrogated the proliferation of
ß T cells, indicating
the need for processing of T. gondii Ags. Analysis of the
TCR Vß expression did not show evidence for restriction in TCR Vß
usage during T. gondii stimulation of
ß T cells.
ß T cells secreted significant amounts of IFN-
after incubation
with T. gondii-infected monocytes. This rapid and
remarkable
ß T cell response may play an important role in the
early events of the immune response to T. gondii.
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