CD8+ cytotoxic T cells induce relapsing colitis in normal mice

Area of Science:

• Immunology
• Gastroenterology
• T cell biology

Background:

• Most inflammatory bowel disease (IBD) mouse models focus on CD4+ T cells.
• A need exists for models investigating CD8+ T cell roles in colitis.

Purpose of the Study:

• To develop an antigen-specific relapsing colitis model.
• To compare the roles of CD4+ and CD8+ T cells in colitis initiation.

Main Methods:

• Induction of delayed-type hypersensitivity using 2.4 dinitrobenzene sulfonic acid in Balb/C mice.
• Analysis of CD4+ and CD8+ T cell roles via antibody depletion and cell transfer.
• Assessment of effector cell function using immunohistochemistry, flow cytometry, ELISpot, qPCR, and CTL assays.

Main Results:

• Relapsing colitis occurred after challenge in sensitized mice.
• Hapten-specific cytotoxic CD8+ T cells (Tc1) were generated before disease onset.
• CD8+ T cell depletion prevented colitis; CD8+ T cell transfer induced colitis in naive mice.

Conclusions:

• Antigen-specific CD8+ T cells can induce relapsing colitis.
• Cytolytic CD8+ Tc1 activity against epithelial cells may initiate intestinal inflammation.