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,
Departments of
*
Neurology and
Molecular Microbiology and Immunology, Oregon Health Sciences University, and
Department of Veterans Affairs, Neuroimmunology Research, Portland, OR 97201
Adoptive transfer of proteolipid protein 139–151-specific T
cell lines was used to examine the role of androgens in regulating T
cell cytokine secretion and the severity of experimental autoimmune
encephalomyelitis (EAE) in the SJL mouse. In this study, we found that
T cells from female mice transferred more severe EAE than T cells from
male mice and that gender differences in clinical disease were due, at
least in part, to differences in donor T cell cytokine secretion. T
cell lines were selected from proteolipid protein 139–151-immunized
female SJL mice in the presence or absence of exogenous androgens.
Androgen-selected T cell lines secreted less IFN-
and more IL-10
than untreated cell lines. Clinical disease induced by the adoptive
transfer of androgen-selected T cell lines was less severe than disease
induced with untreated T cell lines. Furthermore, androgen treatment of
naive TCR transgenic T cells, during their first encounter with Ag,
resulted in a shift in the balance of Th1/Th2 cytokines. This phenotype
was maintained during subsequent stimulations in the absence of
androgen. These results suggest that androgen present in the lymphoid
microenvironment during the induction of an immune response can alter
the development of effector T cells and may play an important role in
governing gender differences in the immune response and susceptibility
to autoimmune disorders.
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