Dextran sulfate sodium (DSS) induced experimental colitis in immunodeficient mice: effects in CD4(+) -cell depleted, athymic and NK-cell depleted SCID mice.
Administration of dextran sulfate to mice, given in the drinking water results in acute or subacute colonic inflammation, depending on the administration protocol. This colonic inflammation exhibits ulceration, healing and repair, and a therapeutic response that makes it valuable for the study of mechanisms that could act in the pathogenesis of human ulcerative colitis, a disease thought to have an immunologically dependent pathogenesis. To investigate if immunological mechanisms were involved in the induction of colonic inflammation in this model, mice with different degrees of immunodeficiency were used. It was shown that dextran sulfate induced colitis could be induced in Balb/c mice depleted of CD4(+) helper T cells by treatment with monoclonal antibodies preceded by adult thymectomy. The depletion of CD4(+) was verified by flow cytometric analysis. Furthermore, the colonic inflammation could equally be induced in athymic CD-1 nu/nu mice lacking thymus-derived T cells, in T and B-cell deficient SCID mice, and also in SCID mice depleted of NK cells by treatment with anti-asialo GM1 antibodies. The NK-cell depletion was verified by measuring spleen NK-cell activity. The resulting colonic inflammation in all these types of deficient mice was qualitatively comparable, as shown by clinical and histological appearance. These results indicate that the presence of functional T, B and NK cells is not crucial for the induction of dextran sulfate colitis in mice.
Axelsson
L G
LG
Dept. of Zoophysiology, Uppsala University, Sweden.
Landström
E
E
Goldschmidt
T J
TJ
Grönberg
A
A
Bylund-Fellenius
A C
AC
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000998:Antiviral Agents / Q000008:administration & dosage / Q000633:toxicity*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D001835:Body Weight / Q000187:drug effects; D003093:Colitis, Ulcerative / Q000139:chemically induced* / Q000188:drug therapy / Q000276:immunology; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000293:injuries; D016264:Dextran Sulfate / Q000008:administration & dosage / Q000633:toxicity*; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D019085:Fluorescent Antibody Technique, Direct; D005677:G(M1) Ganglioside / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008221:Lymphoid Tissue / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D009929:Organ Size / Q000187:drug effects; D013047:Specific Pathogen-Free Organisms; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D013934:Thymectomy
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D007074:Immunoglobulin G; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D016264:Dextran Sulfate