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Updated: Jul 16, 2025
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Evaluation of T Follicular Helper Cells and Germinal Center Response During Influenza A Virus Infection in Mice
Published on: June 27, 2020
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The guanine nucleotide exchange factor Rin-like controls Tfh cell differentiation via CD28 signaling
Lisa Sandner1, Marlis Alteneder1, Ramona Rica1
1Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
The Journal of Experimental Medicine
|September 13, 2023
Summary
The guanine nucleotide exchange factor (GEF) Rin-like (Rinl) negatively regulates T follicular helper (Tfh) cell generation. Loss of Rinl increases Tfh cells, impacting T cell activation and differentiation via CD28 signaling.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- T follicular helper (Tfh) cells are crucial for adaptive immunity, driving B cell maturation and antibody production.
- Dysregulation of Tfh cell populations is implicated in various immune disorders.
Purpose of the Study:
- To identify novel regulators of T follicular helper (Tfh) cell differentiation.
- To elucidate the molecular mechanisms governing Tfh cell development.
Main Methods:
- Investigated the role of guanine nucleotide exchange factor (GEF) Rin-like (Rinl) in Tfh cell generation.
- Utilized mouse models (aging, immunization, infection) and in vitro human CD4+ T cell cultures.
- Employed adoptive transfer experiments with wild-type (WT) and Rinl-knockout (KO) T cells.
- Analyzed CD28 internalization and signaling pathways.
Main Results:
- Identified Rinl as a negative regulator of Tfh cell differentiation across species.
- Observed increased Tfh cell populations in Rinl-deficient settings (aging, infection, immunization).
- Demonstrated T cell-intrinsic, GEF-dependent functions of Rinl in regulating Tfh generation.
- Linked Rinl to the regulation of CD28 internalization and downstream signaling in CD4+ T cells.
Conclusions:
- Rinl acts as a key negative regulator of Tfh cell differentiation in a manner conserved across species.
- Rinl's function involves modulating CD28 internalization and signaling, highlighting the importance of endocytic processes in Tfh development.
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