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Departments of
*
Microbiology,
Surgery,
Pathology and Laboratory Medicine, and
§
Hematology and Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104
IL-2-deficient (IL-2-/-) mice develop disorders
of the hemopoietic and immune systems characterized by anemia,
lymphocytic hyperplasia, and colitis. The mechanisms responsible for
these abnormalities remain unclear. To investigate the underlying basis
of autoimmunity, the particular role of commensal gut flora in the
initiation of colitis, and the role of IL-2 in the development of
intestinal intraepithelial lymphocytes (iIEL), we evaluated
IL-2-/- mice reared and maintained under gnotobiotic
(germfree) conditions. By 8 wk of age, 80% (20 of 25) of germfree
IL-2-/- mice show signs of disease, including anemia,
disturbances in bone marrow hemopoietic cells, lymphocytic hyperplasia,
and generalized autoimmunity, similar to those seen in specific
pathogen-free (SPF) IL-2-/- mice. In striking contrast to
SPF IL-2-/- mice, germfree IL-2-/- mice do
not develop colitis. However, the numbers of 
+ and
TCR
ß+CD8+ iIELs are reduced, and in
lethally irradiated SPF IL-2+/+ mice, reconstituted with
IL-2-/- bone marrow TCR+ iIELs fail to
develop, consistent with an important role of IL-2/IL-2R signaling in
the development of iIELs. Consequently, our findings demonstrate
that the colitis seen in SPF IL-2-/- mice depends upon
the presence of intestinal bacterial flora and that environmental Ags
are not responsible for the anemia and extraintestinal lymphoid
hyperplasia that occur in IL-2-/- mice. Thus, germfree
IL-2-/- mice represent a unique system in which the role
of IL-2 deficiency in hemopoietic and immune system disorders can be
investigated in dissociation from complications that may arise due to
colitis.
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