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Immunity. 2014 Dec 18;41(6):1013-25. doi: 10.1016/j.immuni.2014.12.006. Epub 2014 Dec 6.

Regulatory T cells control antigen-specific expansion of Tfh cell number and humoral immune responses via the coreceptor CTLA-4.

Author information

1
Laboratory of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan.
2
Laboratory of Lymphocyte Differentiation, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan.
3
Laboratory of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan; Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan. Electronic address: shimon@ifrec.osaka-u.ac.jp.

Abstract

CD4(+)Foxp3-expressing Treg cells, which constitutively express the inhibitory coreceptor CTLA-4, are indispensable for immune homeostasis. We determined the roles of Treg cells and T follicular regulatory (Tfr) cells in the control of humoral immune responses. Depletion of Treg cells, blocking of CTLA-4 or a Treg cell specific reduction in CTLA-4 expression, resulted in an increase in the formation of antigen-specific Tfh cells, germinal center (GC), and plasma and memory B cells after vaccination. In the absence of Treg cell-expressed CTLA-4, large numbers of Tfr cells were present but were unable to restrain Tfh cell and GC formation. Temporary Treg cell depletion during primary immunization was sufficient to enhance secondary immune responses. Treg cells directly inhibited, via CTLA-4, B cell expression of CD80 and CD86, which was essential for Tfh cell formation. Thus, Treg and Tfr cells control Tfh cell and germinal center development, via CTLA-4-dependent regulation of CD80 and CD86 expression.

PMID:
25526312
DOI:
10.1016/j.immuni.2014.12.006
[Indexed for MEDLINE]
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