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Isolation of CD4+ T-cells and Analysis of Circulating T-follicular Helper (cTfh) Cell Subsets from Peripheral Blood Using 6-color Flow Cytometry
Published on: January 7, 2019
Follicular helper T cells are required for systemic autoimmunity
Michelle A Linterman1, Robert J Rigby, Raphael K Wong
1Division of Immunology and Genetics, The John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia.
The Journal of Experimental Medicine
|February 18, 2009
Summary
Aberrant selection of germinal center (GC) B cells, driven by dysfunctional follicular helper T (T(FH)) cells, promotes lupus autoimmunity. Targeting T(FH) cell dysfunction offers a potential therapeutic strategy for systemic autoimmune diseases.
Area of Science:
- Immunology
- Autoimmunity
- Molecular Biology
Background:
- High-affinity autoantibodies are central to lupus pathogenesis.
- Germinal centers (GCs) are critical for normal antibody production.
- Aberrant GC B cell selection, possibly due to follicular helper T (T(FH)) cells, may explain autoantibody formation in lupus.
Purpose of the Study:
- To investigate the role of Roquin-san allele in GC B cell selection and autoantibody production.
- To determine if T(FH) cell dysfunction contributes to lupus pathogenesis in Roquin-san mice.
- To identify potential therapeutic targets for lupus autoimmunity.
Main Methods:
- Utilized Roquin(san/san) mice, a model for lupus autoimmunity.
- Examined the impact of Bcl6 and Sap gene alterations on GC formation and T(FH) cell numbers.
- Performed adoptive transfer of T(FH) cells to assess their role in GC formation.
Main Results:
- Autoimmunity in Roquin-san mice is dependent on GC formation, as Bcl6 heterozygosity ameliorates pathology.
- Roquin-san directly causes T(FH) cell accumulation.
- Disruption of Sap function selectively reduces T(FH) cells, abrogating GC formation, autoantibody production, and kidney pathology.
- Adoptive transfer of Roquin-san T(FH) cells induces spontaneous GC formation.
Conclusions:
- T(FH) cell dysfunction within GCs is a key driver of systemic autoimmunity.
- Aberrant positive selection in GCs, mediated by T(FH) cells, contributes to lupus pathogenesis.
- Targeting T(FH) cell dysfunction presents a promising therapeutic avenue for lupus and related autoimmune diseases.
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