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*
Research Institute, Palo Alto Medical Foundation, Palo Alto, CA 94301;
Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, OH 45267; and
DNAX Research Institute of Molecular and Cellular Biology, Inc., Palo Alto, CA 94304
The costimulatory ligands CD80 and CD86 play a crucial role in the
initiation and maintenance of an immune response. We demonstrate that
whereas infection of human monocytes with viable tachyzoites of
Toxoplasma gondii resulted in rapid induction of expression
of CD80 and up-regulation of expression of CD86, incubation with killed
organisms failed to alter the levels of expression of these
costimulatory ligands. The T. gondii-mediated changes in
levels of expression of these molecules are critical to the T cell
response to the parasite. Proliferation of resting T cells in response
to parasite-infected cells was dependent on both CD80 and CD86. More
importantly, early production of IFN-
in response to T.
gondii by T cells from T. gondii-seronegative
individuals occurred only after stimulation with monocytes that
exhibited increased expression of CD80 and CD86 (monocytes infected
with viable parasites) and was almost completely ablated by the
combination of anti-CD80 plus anti-CD86 mAb. Moreover,
proliferation and IFN- production by CD4+
CD45RA+ T cells from unexposed individuals were dependent
on both CD80 and CD86. These data indicate that pathogen-monocyte
interaction influences the ensuing T cell response.
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