Colitogenic CD4+ effector-memory T cells actively recirculate in chronic colitic mice

Area of Science:

• Immunology
• Gastroenterology
• T cell biology

Background:

• Leukocytapheresis shows clinical utility in inflammatory bowel disease (IBD) by removing pathogenic immune cells.
• The continuous circulation of colitogenic CD4(+) T cells in peripheral blood during chronic colitis remains unestablished.

Purpose of the Study:

• To investigate the recirculation dynamics of colitogenic CD4(+) T cells in a murine model of chronic colitis.
• To determine if peripheral blood CD4(+) T cells from colitic mice can induce colitis upon transfer.

Main Methods:

• Adoptive transfer of CD4(+)CD45RB(high) cells into SCID mice to induce chronic colitis.
• Utilized a parabiosis system to assess T cell recirculation between established colitic and healthy mice.
• Investigated the effect of FTY720 on T cell redistribution in parabionts.

Main Results:

• Colitogenic CD4(+)CD45RB(high) cells differentiate into effector-memory T (T(EM)) cells and distribute systemically in colitic mice.
• Peripheral blood CD4(+) T cells from colitic mice induced identical colitis upon retransfer.
• CD4(+) T cells showed significant mixing between parabionts, which was inhibited by FTY720.

Conclusions:

• Colitogenic CD4(+) T(EM) cells continuously recirculate throughout the body in established colitis.
• Therapeutic strategies targeting systemic CD4(+) T(EM) cells, like bone marrow transplantation, are potential IBD treatments.
• Targeting systemic rather than solely intestinal CD4(+) T cells may be more effective for IBD management.