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Follicular regulatory T cells repress cytokine production by follicular helper T cells and optimize IgG responses in mice.
- Source :
-
European journal of immunology [Eur J Immunol] 2016 May; Vol. 46 (5), pp. 1152-61. Date of Electronic Publication: 2016 Mar 11. - Publication Year :
- 2016
-
Abstract
- Follicular helper T (Tfh) cells provide crucial help to germinal center B (GCB) cells for proper antibody production, and a specialized subset of regulatory T cells, follicular regulatory T (Tfr) cells, modulate this process. However, Tfr-cell function in the GC is not well understood. Here, we define Tfr cells as a CD4(+) Foxp3(+) CXCR5(hi) PD-1(hi) CD25(low) TIGIT(high) T-cell population. Furthermore, we have used a novel mouse model ("Bcl6FC") to delete the Bcl6 gene in Foxp3(+) T cells and thus specifically deplete Tfr cells. Following immunization, Bcl6FC mice develop normal Tfh- and GCB-cell populations. However, Bcl6FC mice produce altered antigen-specific antibody responses, with reduced titers of IgG and significantly increased IgA. Bcl6FC mice also developed IgG antibodies with significantly decreased avidity to antigen in an HIV-1 gp120 "prime-boost" vaccine model. In an autoimmune lupus model, we observed strongly elevated anti-DNA IgA titers in Bcl6FC mice. Additionally, Tfh cells from Bcl6FC mice consistently produce higher levels of Interferon-γ, IL-10 and IL-21. Loss of Tfr cells therefore leads to highly abnormal Tfh-cell and GCB-cell responses. Overall, our study has uncovered unique regulatory roles for Tfr cells in the GC response.<br /> (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Subjects :
- Animals
Antibody Affinity
Autoimmunity
Cytokines immunology
DNA immunology
Forkhead Transcription Factors analysis
HIV Antibodies biosynthesis
HIV Antibodies immunology
HIV Envelope Protein gp120 immunology
HIV Envelope Protein gp120 metabolism
Immunoglobulin A biosynthesis
Immunoglobulin A immunology
Immunoglobulin G biosynthesis
Interferon-gamma immunology
Interleukin-10 immunology
Interleukins immunology
Lupus Erythematosus, Systemic immunology
Mice
Proto-Oncogene Proteins c-bcl-6 deficiency
Proto-Oncogene Proteins c-bcl-6 genetics
T-Lymphocytes, Regulatory physiology
Vaccination
Cytokines biosynthesis
Germinal Center immunology
Immunoglobulin G immunology
T-Lymphocytes, Helper-Inducer immunology
T-Lymphocytes, Regulatory immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1521-4141
- Volume :
- 46
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- European journal of immunology
- Publication Type :
- Academic Journal
- Accession number :
- 26887860
- Full Text :
- https://doi.org/10.1002/eji.201546094