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Gut mucosal mast cells. Origin, traffic, and differentiation.
The Journal of Experimental Medicine
|July 1, 1984
Summary
Gut mucosal mast cells (MMC) precursors migrate to the gut and mature into abundant MMC during nematode infection, a process influenced by IL-3 and local factors. This immune response involves T cell activation and cell trafficking for widespread defense.
Area of Science:
- Immunology
- Gastroenterology
- Cell Biology
Background:
- Gut mucosal mast cells (MMC) are scarce in normal mice but increase significantly during nematode infections.
- Mast cell precursors (MMC-P) are abundant in bone marrow and gut, with low frequency in lymphoid organs and thoracic duct lymph (TDL).
- Gut MMC-P are Thy-1- Lyt-1-2- and not rapidly replicating in normal mice.
Purpose of the Study:
- To investigate the origin, migration, and differentiation of gut mucosal mast cells (MMC) and their precursors (MMC-P).
- To understand the role of Interleukin-3 (IL-3) and T cells in MMC development during nematode infection.
- To elucidate the homing mechanisms and maturation process of MMC in the gut mucosa.
Main Methods:
- Limiting dilution assays to determine MMC-P frequency in various tissues.
- Flow cytometry (Thy-1, Lyt-1, Lyt-2 markers) to characterize MMC-P.
- Studies in germ-free, nude, and newborn mice to assess antigen and T cell independence.
- Experiments using tumor-bearing mice (Wehi 3) for IL-3 induction.
- Nematode (Nippostrongylus brasiliensis - Nb) infection models.
- Analysis of cell traffic via thoracic duct lymph (TDL) and fetal gut grafts.
- Transfer experiments in rats.
Main Results:
- MMC-P are attracted from the blood to the gut mucosa by local factors, independent of antigen and T cells.
- IL-3, released by gut mucosal Thy-1+ Lyt-2- cells in Nb-infested mice, induces MMC-P proliferation.
- Nb-stimulated T blasts and MMC-P traffic cyclically into TDL and then seed the gut, facilitating widespread immune defense.
- Continuous homing of T blasts to the gut is essential for full MMC maturation, driven by sustained IL-3 release.
- Circulating TDL MMC-P rapidly mature into MMC upon homing to the Nb-infested gut.
Conclusions:
- Gut MMC arise through progressive differentiation of MMC-P, influenced by IL-3 and local gut factors.
- T cell-dependent IL-3 production and cyclic cell trafficking are crucial for the development and maturation of gut MMC during nematode infection.
- The findings suggest a multi-stage differentiation process for gut MMC, involving both systemic and local regulatory mechanisms.