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Immunity. 2015 Apr 21;42(4):704-18. doi: 10.1016/j.immuni.2015.03.002. Epub 2015 Mar 31.

T follicular helper cells have distinct modes of migration and molecular signatures in naive and memory immune responses.

Author information

1
Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine, UNSW Australia, 390 Victoria Street, Darlinghurst, NSW 2010, Australia.
2
Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia.
3
Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia; St Vincent's Centre for Applied Medical Research, 405 Liverpool Street, Darlinghurst, NSW 2010 Australia.
4
Kyoto University Graduate School of Medicine, Yoshida-honmachi, Sakyo-ku, Kyoto 606-8501, Japan.
5
University of Tsukuba, Ibaraki Prefecture, Tsukuba 305-8572, Japan.
6
St Vincent's Centre for Applied Medical Research, 405 Liverpool Street, Darlinghurst, NSW 2010 Australia.
7
Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine, UNSW Australia, 390 Victoria Street, Darlinghurst, NSW 2010, Australia. Electronic address: t.chtanova@garvan.org.au.
8
Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine, UNSW Australia, 390 Victoria Street, Darlinghurst, NSW 2010, Australia. Electronic address: t.phan@garvan.org.au.

Abstract

B helper follicular T (Tfh) cells are critical for long-term humoral immunity. However, it remains unclear how these cells are recruited and contribute to secondary immune responses. Here we show that primary Tfh cells segregate into follicular mantle (FM) and germinal center (GC) subpopulations that display distinct gene expression signatures. Restriction of the primary Tfh cell subpopulation in the GC was mediated by downregulation of chemotactic receptor EBI2. Following collapse of the GC, memory T cells persisted in the outer follicle where they scanned CD169(+) subcapsular sinus macrophages. Reactivation and intrafollicular expansion of these follicular memory T cells in the subcapsular region was followed by their extrafollicular dissemination via the lymphatic flow. These data suggest that Tfh cells integrate their antigen-experience history to focus T cell help within the GC during primary responses but act rapidly to provide systemic T cell help after re-exposure to the antigen.

PMID:
25840682
DOI:
10.1016/j.immuni.2015.03.002
[Indexed for MEDLINE]
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