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and Immunopathology During Infection with Toxoplasma gondii1
,
*
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104;
Wistar Institute, Philadelphia, PA 19104; and
The Ludwig Institute for Cancer Research, New York, NY 10058
The interaction of activated CD44 with its ligand, low m.w.
hyaluronan, is involved in inflammation, but no role has been
identified for this interaction in the regulation of an immune response
to infection. In these studies, infection of C57BL/6 mice with
Toxoplasma gondii resulted in increased expression of
CD44 on T cells, B cells, NK cells, and macrophages, and a small
percentage of CD4+ T cells express an activated form of
CD44. Administration of anti-CD44 to infected mice prevented the
development of a CD4+ T cell-dependent, infection-induced
inflammatory response in the small intestine characterized by the
overproduction of IFN-
. The protective effect of anti-CD44
treatment was associated with reduced production of IFN-, but not
IL-12, in vivo and in vitro. Furthermore, the addition of low m.w.
hyaluronan to cultures of splenocytes or purified CD4+ T
cells from infected mice resulted in the production of high levels of
IFN-, which was dependent on IL-12 and TCR stimulation. Together,
these results identify a novel role for CD44 in the regulation of
IFN- production by CD4+ T cells during infection and
demonstrate a role for CD44 in the regulation of infection-induced
immune pathology.
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