Resident CD4+ T cells accumulate in lymphoid organs after prolonged antigen exposure

Ugur, Milas; Schulz, Olga; Menon, Manoj B.; Krueger, Andreas; Pabst, Oliver

doi:10.1038/ncomms5821

Cited by 60 publications

(70 citation statements)

References 26 publications

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“…Our study extends previous work that addressed the migratory capacity of T FH , both within and outside the LN (14,15,(17)(18)(19), by demonstrating the inability of early differentiating T FH to egress from the initial activation LN, which is likely regulated by the interplay between CD69 and S1P 1 . Notably, this T FH bias toward primary LNs preceded a similar anatomical bias of the humoral immune response with much more pronounced accumulation of GC B cells in primary LNs.…”

Section: Bcl6supporting

confidence: 69%

“…Retention of T FH in reactive lymphoid tissues is likely a consequence of the local milieu and the long-term persistence of Ag (14,15). In this scenario, T FH retention and continuous exposure to T FH inducing signals may be driven by such T cellextrinsic factors rather than an inherent inability of T FH to egress from LNs.…”

Section: T Follicular Helper Cells (T Fh )mentioning

confidence: 99%

“…In several experimental systems T FH demonstrate a lymphoidresident, nonmigratory phenotype (14)(15)(16). Despite this, T FH can migrate between distinct germinal centers (GCs) within the same lymph node (LN) (17), and several studies have demonstrated the existence of circulating CXCR5…”

Section: T Follicular Helper Cells (T Fh )mentioning

confidence: 99%

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Limited Internodal Migration of T Follicular Helper Cells after Peripheral Infection with Herpes Simplex Virus-1

Stankovic

Harpur

MacLeod

et al. 2015

The Journal of Immunology

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The ability of CD4 T cells to give rise to specialized T follicular helper cells (TFH) critical to initiating appropriate Ab responses is regulated by environmental cues in lymphoid tissues draining the site of infection. In this study, we used a skin infection with HSV-1 characterized by the successive involvement of interconnected but distinct lymph nodes (LNs), to investigate the anatomical diversification of virus-specific CD4 T cell responses and the migratory capacity of TFH or their precursors. Whereas Th1 effector CD4 T cells expressing peripheral-targeting migration molecules readily migrated from primary to secondary reactive LNs, Bcl6+ CXCR5+ PD1hi TFH were largely retained at the site of initial activation with little spillover into the downstream LNs involved at later stages of infection. Consistent with this, TFH maintained high-level surface expression of CD69, indicative of impaired migratory capacity. Notably, the biased generation and retention of TFH in primary LNs correlated with a preferential generation of germinal centers at this site. Our results highlight a limited anatomical diversification of TFH responses and germinal center reactions that were imprinted within the first few cell divisions during TFH differentiation in LNs draining the site of initial infection.

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Section: Bcl6supporting

confidence: 69%

Section: T Follicular Helper Cells (T Fh )mentioning

confidence: 99%

See 1 more Smart Citation

Limited Internodal Migration of T Follicular Helper Cells after Peripheral Infection with Herpes Simplex Virus-1

Stankovic

Harpur

MacLeod

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…To explore this idea, we quantified the recirculation rates of naive and memory B cells between PPs and spleen. To track B cell egress from PPs, we marked cells in situ in PPs by photoconversion as described 22,23 . We generated bone marrow-chimeric mice expressing the photoconvertible protein Dendra2 in hematopoietic cells (Dendra2 chimera).…”

Section: Memory Responses Generate Extraintestinal Plasma Cellsmentioning

confidence: 99%

Diversification of memory B cells drives the continuous adaptation of secretory antibodies to gut microbiota

Lindner¹,

Thomsen²,

Wahl³

et al. 2015

Nat Immunol

Self Cite

192

194

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Secretory immunoglobulin A (SIgA) shields the gut epithelium from luminal antigens and contributes to host-microbe symbiosis. However, how antibody responses are regulated to achieve sustained host-microbe interactions is unknown. We found that mice and humans exhibited longitudinal persistence of clonally related B cells in the IgA repertoire despite major changes in the microbiota during antibiotic treatment or infection. Memory B cells recirculated between inductive compartments and were clonally related to plasma cells in gut and mammary glands. Our findings suggest that continuous diversification of memory B cells constitutes a central process for establishing symbiotic host-microbe interactions and offer an explanation of how maternal antibodies are optimized throughout life to protect the newborn.

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“…Tfh cells can remain for many months in the original draining lymph node where persistent antigen is likely to maintain them in an active state. These cells rapidly expand upon re‐challenge and may represent a population of lymph node resident memory cells as they can express CD69 58, 59, 60. However, this reliance on antigen suggests that these lymph node resident Tfh cells may not represent ‘true resting memory cells’.…”

Section: Memory Cd4 T‐cells Are Found Throughout the Bodymentioning

confidence: 99%

The roles of resident, central and effector memory CD4 T‐cells in protective immunity following infection or vaccination

2018

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SummaryImmunological memory provides rapid protection to pathogens previously encountered through infection or vaccination. CD4 T‐cells play a central role in all adaptive immune responses. Vaccines must, therefore, activate CD4 T‐cells if they are to generate protective immunity. For many diseases, we do not have effective vaccines. These include human immunodeficiency virus (HIV), tuberculosis and malaria, which are responsible for many millions of deaths each year across the globe. CD4 T‐cells play many different roles during the immune response coordinating the actions of many other cells. In order to harness the diverse protective effects of memory CD4 T‐cells, we need to understand how memory CD4 T‐cells are generated and how they protect the host. Here we review recent findings on the location of different subsets of memory CD4 T‐cells that are found in peripheral tissues (tissue resident memory T‐cells) and in the circulation (central and effector memory T‐cells). We discuss the generation of these cells, and the evidence that demonstrates how they provide immune protection in animal and human challenge models.

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Resident CD4+ T cells accumulate in lymphoid organs after prolonged antigen exposure

Cited by 60 publications

References 26 publications

Limited Internodal Migration of T Follicular Helper Cells after Peripheral Infection with Herpes Simplex Virus-1

Limited Internodal Migration of T Follicular Helper Cells after Peripheral Infection with Herpes Simplex Virus-1

Diversification of memory B cells drives the continuous adaptation of secretory antibodies to gut microbiota

The roles of resident, central and effector memory CD4 T‐cells in protective immunity following infection or vaccination

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