       Document 0641
 DOCN  M9620641
 TI    Evidence that CD4+, but not CD8+ T cells are responsible for murine
       interleukin-2-deficient colitis.
 DT    9602
 AU    Simpson SJ; Mizoguchi E; Allen D; Bhan AK; Terhorst C; Division of
       Immunology Beth Israel Hospital, Harvard Medical; School, Boston, MA
       02215, USA.
 SO    Eur J Immunol. 1995 Sep;25(9):2618-25. Unique Identifier : AIDSLINE
       MED/96011876
 AB    Mice deficient in interleukin-2 production (IL-2null mice) develop
       colonic inflammation closely resembling ulcerative colitis in humans.
       Although this disease is marked by substantial infiltration of the colon
       by CD8+ and CD4+ T lymphocytes, no function has yet been assigned to
       these T cell subsets in the development of colitis in the IL-2null
       mouse. For the present study, we investigated the involvement of T
       lymphocytes in the onset of colitis in IL-2null mice, and examined the
       possible role played by cytotoxic T cells. Both lamina propria
       lymphocytes (LPL) and intraepithelial lymphocytes (IEL) of the colon of
       IL-2null mice were potently cytotoxic ex vivo in short-term redirected
       cytotoxic lymphocyte (CTL) assays. In contrast, colonic T cells of
       wild-type animals showed little or no constitutive cytotoxic T cell
       activity. Colonic CTL were detectable prior to the appearance of disease
       in IL-2null animals and CTL activity was confined to the TcR alpha beta,
       rather than to the TcR gamma delta IEL subset. IL-2null animals crossed
       with major histocompatibility complex class I-deficient mice [IL-2null x
       beta 2 microglobulin (beta 2mnull) mice] also developed colitis, which
       appeared even earlier than in most IL-2null mice. These findings suggest
       that neither CD8+ IEL nor LPL were causal in the onset of colitis in
       IL-2null animals. In IL-2null x beta 2mnull mice, an ulcerative
       colitis-like disease was evident from histological studies and
       immunohistological staining which showed very large numbers of CD4+
       lymphocytes within the intestinal mucosa. Significant ex vivo killing by
       CD4+ T cells was observed in IL-2null x beta 2null animals, although
       this required an extended incubation time compared to colonic CD8+ T
       cells. Peripheral as well as colonic CD4+ T cells in IL-2null and
       IL-2null x beta 2mnull animals, were activated as judged by their cell
       surface phenotype (CD45RBlo, L-selectinlo and CD69+). In light of these
       findings, we propose that infiltrating CD4+, but not CD8+ T cells are
       central to the inflammation observed in the intestinal mucosa in
       IL-2null colitis.
 DE    Animal  Colitis, Ulcerative/*IMMUNOLOGY  Colon/IMMUNOLOGY  Cytotoxicity,
       Immunologic  CD4-Positive T-Lymphocytes/*IMMUNOLOGY  CD8-Positive
       T-Lymphocytes/*IMMUNOLOGY  Disease Models, Animal
       Interleukin-2/*DEFICIENCY  Mice  Mice, Inbred C57BL  Support, Non-U.S.
       Gov't  Support, U.S. Gov't, P.H.S.  T-Lymphocyte Subsets  JOURNAL
       ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

