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Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets

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Published on: April 16, 2015

Extrathymically generated regulatory T cells control mucosal TH2 inflammation.

Steven Z Josefowicz¹, Rachel E Niec, Hye Young Kim

¹Howard Hughes Medical Institute and Immunology Program, Sloan Kettering Institute, New York, New York 10021, USA.

|February 10, 2012

Summary

Induced regulatory T (Treg) cells, not thymus-derived ones, are crucial for preventing allergic inflammation at mucosal sites and maintaining gut microbiota balance. Their deficiency leads to allergic conditions like asthma.

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Area of Science:

Immunology
Microbiology

Background:

Mucosal interfaces require a balance of pro- and anti-inflammatory responses for pathogen defense without causing allergy or inflammation.
Regulatory T (Treg) cells, originating from the thymus (tTreg) or periphery (iTreg), are vital for immune homeostasis and preventing autoimmunity.

Purpose of the Study:

To investigate the distinct roles of thymus-derived (tTreg) and induced (iTreg) regulatory T cells in maintaining immune balance at mucosal surfaces.
To determine if iTreg cells are essential for preventing allergic inflammation and maintaining gut microbiota composition.

Main Methods:

Selective blockage of induced regulatory T (iTreg) cell differentiation in mice.
Assessment of autoimmune pathology, T helper cell responses (T(H)1, T(H)17, T(H)2), and mucosal inflammation.
Analysis of gut microbial community composition in iTreg-deficient mice.

Main Results:

Mice lacking iTreg cells did not develop systemic autoimmunity or exacerbated T(H)1/T(H)17 responses.
iTreg cell deficiency led to significant T(H)2-type allergic inflammation in the gastrointestinal tract and lungs.
Absence of iTreg cells altered the composition of the gut microbiota.

Conclusions:

Thymus-derived Treg cells are sufficient for controlling systemic autoimmunity.
Extrathymic iTreg cells play a critical, distinct role in suppressing mucosal allergic inflammation and modulating gut microbiota.
Understanding iTreg cell function is key to addressing allergic diseases and gut dysbiosis.