Autoimmune intestinal pathology induced by hsp60-specific CD8 T cells

Area of Science:

• Immunology
• Autoimmune Diseases
• Gastroenterology

Background:

• Heat shock proteins (hsp) are structurally similar and widely distributed, making them potential targets in autoimmune conditions.
• CD8 T cells play a critical role in immune responses and can be involved in the pathogenesis of inflammatory diseases.

Purpose of the Study:

• To investigate the role of heat shock protein 60 (hsp60)-reactive CD8 T cells in inducing intestinal inflammation.
• To elucidate the mechanisms underlying hsp60-induced gut inflammation and its connection to autoimmune processes.

Main Methods:

• Transfer of hsp60-reactive CD8 T cells into recipient mice.
• Analysis of inflammatory markers, including Interferon gamma (IFN-γ) and Tumor Necrosis Factor alpha (TNF-α).
• Assessment of pathology in both conventional and germ-free mice, and in mice lacking TNF-α receptors.

Main Results:

• Induction of MHC class I-dependent intestinal inflammation, primarily in the small intestine, following T cell transfer.
• Elevated levels of IFN-γ, TNF-α, and gut-derived hsp60 at sites of T cell infiltration.
• Significant reduction in intestinal lesions in mice lacking TNF-α receptors, and development of pathology in germ-free mice.

Conclusions:

• CD8 T cells with specific antigen recognition can directly cause intestinal inflammation.
• Host-derived hsp60 is recognized by CD8 T cells, suggesting a role in autoimmune pathogenesis.
• This study highlights a potential link between infections and the development of autoimmune-mediated intestinal diseases.