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Lymphoid reservoirs of antigen-specific memory T helper cells

Nature Immunology volume 8, pages 753–761 (2007)Cite this article

Abstract

How vaccines control the development of antigen-specific effector and memory T helper cells is central to protective immunity but remains poorly understood. Here we found that protein vaccination selected high-affinity, CXCR5+ICOShi follicular B-helper T cells (TFH cells) that developed in draining lymphoid tissue to regulate B cell responses. In the memory phase, reservoirs of antigen-specific CXCR5+ICOSlo TFH cells persisted with less effector activity but accelerated antigen-recall ability. This new compartment of memory TFH cells was retained in draining lymphoid sites with antigen-specific memory B cells, persistent complexes of peptide and major histocompatibility complex class II and continued expression of CD69. Thus, protein vaccination promotes B cell immunity by selecting high-affinity effector TFH cells and creating lymphoid reservoirs of antigen-specific memory TFH cells in vivo.

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Figure 1: Selection of high-affinity T helper clones in local lymphoid microenvironments.
Figure 2: Local vaccination induces effector TFH cells in draining lymphoid tissues.
Figure 3: PCC-specific memory T helper cells accumulate in draining lymphoid tissues.
Figure 4: Lymphoid reservoirs of high-affinity PCC-specific memory TFH cells.
Figure 5: Lymphoid reservoirs of antigen-specific memory B cells.
Figure 6: Local depots of peptide–MHC class II persist only in the draining lymphoid tissues.
Figure 7: CD69 expression on antigen-specific memory TFH cells.

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Acknowledgements

We thank D. Nemazee, W. Havran and L. Sherman for critical appraisal of the manuscript; J. Shandraw for technical assistance; M. Davis (Stanford University) for the original 5C.C7αβ transgenic mice and the I-Ek tetramer Escherichia coli–expressed preparations; and B. Blazar (University of Minnesota) for the original B10.BR-Thy-1.1 congenic mice. Supported by the National Institutes of Health (AI47231, AI040215 and AI059475 to M.G.M.-W.), the National Institutes of Health National Service Research Award (M.D.E.), the European Molecular Biology Organization (L.M.) and the Arthritis Foundation (R.R.P.-C). This is manuscript 18458 from The Scripps Research Institute.

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Author notes

  1. Michael D Eisenbraun & Rebecca R Pogue-Caley

    Present address: Present addresses: MedImmune Vaccines, Mountain View, California 94043, USA (M.D.E.), and INC Research, Raleigh, North Carolina 27609, USA (R.R.P.-C.).,

  2. Nicolas Fazilleau and Michael D Eisenbraun: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Immunology, The Scripps Research Institute, La Jolla, California, USA

    Nicolas Fazilleau, Michael D Eisenbraun, Laurent Malherbe, Louise J McHeyzer-Williams & Michael G McHeyzer-Williams

  2. Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA

    Jessica N Ebright & Rebecca R Pogue-Caley

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Correspondence to Michael G McHeyzer-Williams.

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Supplementary information

Supplementary Fig. 1

Dynamics of LN and spleen response to subcutaneous-priming with PCC. (PDF 729 kb)

Supplementary Fig. 2

LN and spleen response to intraperitoneal-priming with PCC. (PDF 542 kb)

Supplementary Fig. 3

CFA induces PCC-specific effector TFH cells in draining LN. (PDF 930 kb)

Supplementary Fig. 4

HEL induces antigen-specific effector TFH in draining LN. (PDF 804 kb)

Supplementary Fig. 5

NP-KLH induces antigen-specific B cell response in draining LN (day 14). (PDF 1558 kb)

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Fazilleau, N., Eisenbraun, M., Malherbe, L. et al. Lymphoid reservoirs of antigen-specific memory T helper cells. Nat Immunol 8, 753–761 (2007). https://doi.org/10.1038/ni1472

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