Antigen-specific CD8 T cells accumulate and functionally reactivate in the bone marrow following brain infection.
13 affiliations
- 1Department of Neurosurgery, Duke University, Durham, NC, 27710, USA.
- 2Department of Immunology, Mayo Clinic, Rochester, MN, 55905, USA.
- 3Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC, 27710, USA.
- 4Department of Integrative Immunobiology, Duke University, Durham, NC, 27710, USA.
- 5Department of Molecular Medicine, Mayo Clinic, Rochester, MN, 55905, USA.
- 6Virology and Gene Therapy Track, Mayo Clinic Graduate School of Biomedical Sciences, Rochester, MN, 55905, USA.
- 7Division of Veterinary Medicine, Paul-Ehrlich-Institute, 63225, Langen, Germany.
- 8Department of Pathology, Duke University, Durham, NC, 27710, USA.
- 9Department of Neurology, Mayo Clinic, Rochester, MN, 55905, USA.
- 10Department of Neurosurgery, Duke University, Durham, NC, 27710, USA. [email protected].
- 11Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC, 27710, USA. [email protected].
- 12Department of Pathology, Duke University, Durham, NC, 27710, USA. [email protected].
- 13Department of Immunology, Mayo Clinic, Rochester, MN, 55905, USA. [email protected].
Abstract
Background
Bone marrow is a primary immune organ responsible for hematopoiesis, yet its role in shaping adaptive immune responses remains incompletely understood. In particular, whether antigen-specific CD8 T cell responses can arise and persist within the bone marrow following brain infection is unclear.Methods
We used intracranial infection with Theiler's Murine Encephalomyelitis Virus (TMEV) in C57BL/6 mice, along with complementary antigen delivery (OVA + Poly I:C) and systemic infection (LCMV) models. Antigen-specific CD8 T cells were quantified in the brain, secondary lymphoid organs, and bone marrow using tetramer-based flow cytometry. Lymphocyte trafficking was modulated using FTY720, and functional memory responses were assessed via peptide reactivation. Hematopoietic stem and progenitor cell (HSPC) populations and myeloid compartments were analyzed by flow cytometry.Results
Antigen-specific CD8 T cells accumulated in the bone marrow within 5-7 days following intracranial TMEV infection, with kinetics comparable to secondary lymphoid organs. Antigen was detectable in the bone marrow within 24 h of intracranial delivery and was primarily associated with migratory antigen-presenting cells. Antigen-specific CD8 T cells persisted long-term in the bone marrow and demonstrated robust expansion upon antigen re-encounter, even under conditions limiting lymphocyte egress. Reactivation of these cells was associated with expansion of Lineage⁻Sca-1⁺c-Kit⁺ (LSK) HSPCs and increased MHCII⁺ myeloid populations. This increase in the LSKs and MHCII + myeloid cells in the bone marrow niche was abrogated with CD8 T cell depletion.Conclusions
These findings establish the bone marrow as an active site of antigen-specific CD8 T cell accumulation, persistence, and functional reactivation following brain infection. Antigen-specific CD8 T cell activity within the bone marrow is associated with modulation of the hematopoietic niche, highlighting a previously underappreciated link between CNS-directed immune responses and systemic hematopoiesis.
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BibTeX
@article{ananiwolf2026antigenspecific,
title = {{Antigen-specific CD8 T cells accumulate and functionally reactivate in the bone marrow following brain infection.}},
author = {Delaney M Anani-Wolf and Eliese M Moelker and Shannon E Wallace and Rachael A Reesman and Kelly M Hotchkiss and Kathryn E Blethen and Saskia Hemmers and Christian K Pfaller and Anna L Borchers and Pamela K Norberg and Brittany N Thomas and Michelle L Bowie and Asma Hassani and Michael D Forston and Alexandra M Hoyt-Miggelbrink and Cori E Fain and Vatsal Jain and Mustafa Khasraw and Gerald A Grant and Vidyalakshmi Chandramohan and Aaron J Johnson and Katayoun Ayasoufi},
journal = {Journal of neuroinflammation},
year = {2026},
month = jul,
doi = {10.1186/s12974-026-03968-z},
url = {https://europepmc.org/article/MED/42894239},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Antigen-specific CD8 T cells accumulate and functionally reactivate in the bone marrow following brain infection.
AU - Delaney M Anani-Wolf
AU - Eliese M Moelker
AU - Shannon E Wallace
AU - Rachael A Reesman
AU - Kelly M Hotchkiss
AU - Kathryn E Blethen
AU - Saskia Hemmers
AU - Christian K Pfaller
AU - Anna L Borchers
AU - Pamela K Norberg
AU - Brittany N Thomas
AU - Michelle L Bowie
AU - Asma Hassani
AU - Michael D Forston
AU - Alexandra M Hoyt-Miggelbrink
AU - Cori E Fain
AU - Vatsal Jain
AU - Mustafa Khasraw
AU - Gerald A Grant
AU - Vidyalakshmi Chandramohan
AU - Aaron J Johnson
AU - Katayoun Ayasoufi
PY - 2026
DA - 2026/07/01
JO - Journal of neuroinflammation
DO - 10.1186/s12974-026-03968-z
UR - https://europepmc.org/article/MED/42894239
AB - Background Bone marrow is a primary immune organ responsible for hematopoiesis, yet its role in shaping adaptive immune responses remains incompletely understood. In particular, whether antigen-specific CD8 T cell responses can arise and persist within the bone marrow following brain infection is unclear.Methods We used intracranial infection with Theiler's Murine Encephalomyelitis Virus (TMEV) in C57BL/6 mice, along with complementary antigen delivery (OVA + Poly I:C) and systemic infection (LCMV) models. Antigen-specific CD8 T cells were quantified in the brain, secondary lymphoid organs, and bone marrow using tetramer-based flow cytometry. Lymphocyte trafficking was modulated using FTY720, and functional memory responses were assessed via peptide reactivation. Hematopoietic stem and progenitor cell (HSPC) populations and myeloid compartments were analyzed by flow cytometry.Results Antigen-specific CD8 T cells accumulated in the bone marrow within 5-7 days following intracranial TMEV infection, with kinetics comparable to secondary lymphoid organs. Antigen was detectable in the bone marrow within 24 h of intracranial delivery and was primarily associated with migratory antigen-presenting cells. Antigen-specific CD8 T cells persisted long-term in the bone marrow and demonstrated robust expansion upon antigen re-encounter, even under conditions limiting lymphocyte egress. Reactivation of these cells was associated with expansion of Lineage⁻Sca-1⁺c-Kit⁺ (LSK) HSPCs and increased MHCII⁺ myeloid populations. This increase in the LSKs and MHCII + myeloid cells in the bone marrow niche was abrogated with CD8 T cell depletion.Conclusions These findings establish the bone marrow as an active site of antigen-specific CD8 T cell accumulation, persistence, and functional reactivation following brain infection. Antigen-specific CD8 T cell activity within the bone marrow is associated with modulation of the hematopoietic niche, highlighting a previously underappreciated link between CNS-directed immune responses and systemic hematopoiesis.
SN - 1742-2094
ER -