CD4+ T cells from IL-10-deficient mice transfer susceptibility to NSAID-induced Rag colitis.
Products of arachidonic acid metabolism are important for mucosal homeostasis, because blockade of this pathway with an NSAID triggers rapid onset of severe colitis in the IL-10 knockout (IL-10(-/-)) model of IBD. Rag mice do not make T or B cells. This study determined whether reconstitution of Rag mice with T cells from IL-10(-/-) mice transferred NSAID colitis susceptibility. Rag mice were reconstituted by intraperitoneal injection with splenocytes from wild-type (WT) or IL-10(-/-) animals. Colitis was induced by using piroxicam and was graded histologically. Isolated lamina propria mononuclear cells (LPMC), lamina propria T cells, and LPMC depleted of T cells from reconstituted Rag mice were studied for cytokine production. Only animals reconstituted with IL-10(-/-) CD4(+) T cells and administered piroxicam developed severe colitis. LPMC from these colitic animals made IFN-gamma, whose production was dependent on T cells. Some IL-10 was produced but only from non-T cells. LPMC from the healthy Rag mice that were reconstituted with WT T cells and were piroxicam resistant made much more IL-10. This was mostly T cell dependent. In conclusion, only CD4(+) T cells from IL-10(-/-) animals leave Rag mice susceptible to NSAID-induced, Th1 colitis. Lamina propria T cells normally make large quantities of IL-10, suggesting that IL-10 from T cells may be protective.
Blum
Arthur M
AM
Division of Gastroenterology (4607 JCP Univ. of Iowa Hospital and Clinics, 200 Hawkins Dr., Iowa City, IA 52242-1009, USA.
Metwali
Ahmed
A
Elliott
David E
DE
Berg
Daniel J
DJ
Weinstock
Joel V
JV
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D017690:Cell Transplantation; D003092:Colitis / Q000139:chemically induced*; D016207:Cytokines / Q000378:metabolism; D004198:Disease Susceptibility; D016753:Interleukin-10 / Q000172:deficiency*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D010894:Piroxicam / Q000009:adverse effects; D013154:Spleen / Q000166:cytology / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D016753:Interleukin-10; D010894:Piroxicam