IL-2 knockout recipient mice reject islet cell allografts.
The IL-2 pathway is portrayed often as central to allograft rejection. To test this hypothesis, we studied IL-2-deficient mice as allograft recipients. IL-2 gene knockout (KO) mice reject islet allografts and demonstrate a classical mononuclear leukocytic infiltrate, containing CD4+ and CD8+ T cells, surrounding and invading the islet allografts. Moreover, allograft rejection in the IL-2 KO mouse is associated with intragraft expression of certain cytokine and CTL attack molecule genes (e.g. IFN-gamma, IL-4, IL-7, IL-10, and granzyme B). In separate experiments, IL-2 KO mice generated CTLs in response to in vivo challenge with allogeneic tumor cells. Although IL-2 KO mice reject allografts in vivo, spleen cells from immunologically naive IL-2 KO mice exhibit a diminished proliferative response to mitogens in vitro that could be restored largely by exogenous IL-2, IL-4, or IL-7. The paradoxical ability to execute graft rejection in vivo despite near absent T cell proliferative responses in vitro may result from the expression of IL-7 in vivo, but not in vitro. Con A-stimulated bulk spleen cell cultures derived from IL-2 KO mice were essentially devoid not only of IL-2 but also IL-7 gene transcripts. These data indicate that 1) IL-2 is not the sole T cell growth factor capable of supporting allograft rejection and 2) expression of IL-4, but not IL-2, during the allograft response does not lead inevitably to tolerance.
Steiger
J
J
Harvard Medical School, Department of Medicine, Beth Israel Hospital, Boston, MA 02215, USA.
Nickerson
P W
PW
Steurer
W
W
Moscovitch-Lopatin
M
M
Strom
T B
TB
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology; D007150:Immunohistochemistry; D007376:Interleukin-2 / Q000494:pharmacology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout / Q000502:physiology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D007376:Interleukin-2