Memory CD4 T Cells That Express CXCR5 Provide Accelerated Help to B Cells

MacLeod, Megan K. L.; David, Alexandria; McKee, Amy S.; Crawford, Frances; Kappler, John W.; Marrack, Philippa

doi:10.4049/jimmunol.1002955

Cited by 127 publications

(121 citation statements)

References 46 publications

Supporting

Mentioning

112

Contrasting

Order By: Relevance

“…found that the number of antigen‐specific memory cells that expressed Tfh markers declined over time, suggesting that Tfh cells fail to differentiate into long‐lived memory cells 57. However, we and others have shown that both mouse and human CXCR5+ memory CD4 T‐cells provide rapid assistance to B‐cells upon reactivation 61, 62, 63, 64, 65, 66, 67, 68, 69. Importantly, Alexander et al .…”

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

confidence: 73%

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

2018

Self Cite

View full text Add to dashboard Cite

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.

show abstract

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

confidence: 73%

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

2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the mouse model of Listeria monocytogenes infection, CXCR5 + PD1 2 CD4 + T cells were found to be the subset of central memory precursors that formed T FH more efficiently than Th1 upon boosting (60). In another study, LCMV-derived 3K peptide plus LPS immunization generated CXCR5 + endogenous CD4 + memory T cells that accelerated the kinetics (expansion/ isotype switching) of cognate naive B cell responses in a subsequent boost with 3K-OVA (61). In this study, we observed higher expression of CXCR5 and PD1 on gD-specific memory cells generated through Clec9A targeting, suggesting formation of T FH memory.…”

Section: Cd8mentioning

confidence: 97%

Targeting Antigen to Clec9A Primes Follicular Th Cell Memory Responses Capable of Robust Recall

Kato

Zaid

Davey

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

Targeting Ags to dendritic cell (DC) surface receptors can induce a variety of responses depending on the DC type targeted, the receptor targeted, and the adjuvant used. Clec9A (DNGR-1), which is expressed by CD8+ DCs, has been shown to bind F-actin exposed on damaged cells. Targeting Ag to this receptor in mice and nonhuman primates induces strong humoral immunity even in the absence of adjuvant, a process seen for a few select DC receptors. In contrast with other receptors, however, targeting Clec9A induces long-lived, affinity-matured Ab responses that are associated with efficient CD4+ T cell responses shown to possess properties of follicular Th cells (TFH). In this article, we provide definitive evidence that Clec9A targeting promotes the development of TFH by showing that responding CD4 T cells express CXCR5, PD1, the TFH transcription factor Bcl6, and the cytokine IL-21, and that these cells localize to germinal centers. Furthermore, we extend studies from the model Ag OVA to the viral Ag glycoprotein D of HSV-1 and examine the capacity of primed TFH to form functional memory. We show that targeting glycoprotein D to Clec9A even in the absence of adjuvant induced long-lived memory CXCR5+ PD1hi CD4+ T cells that proliferated extensively upon secondary challenge and rapidly developed into effector TFH. This was associated with enhanced germinal center B cell responses and accelerated Ab production. Our study indicates that targeting Ags to Clec9A in the absence of adjuvant routinely generates TFH responses that form long-lived memory capable of robust secondary TFH responses.

show abstract

“…A nalyses of the mechanisms underlying memory CD4 + T-cellmediated protection have focused largely on their earlier provision of help as compared with naive cells (1), although it also is appreciated that highly activated secondary CD4 + T-cell (hereafter, 2°) effectors develop after the re-expansion of memory populations (2). Studies also suggest that optimal protection provided by T helper type 1 (T H 1)-like memory CD4 + T cells correlates with the capacity to produce multiple cytokines, including IFN-γ, TNF, and IL-2, rather than IFN-γ alone (3).…”

Section: Cytokines | Viral Infection | Immune Regulationmentioning

confidence: 99%

Memory CD4⁺T-cell–mediated protection depends on secondary effectors that are distinct from and superior to primary effectors

Strutt

McKinstry

Kuang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

112

View full text Add to dashboard Cite

Whether differences between naive cell-derived primary (1°) and memory cell-derived secondary (2°) CD4+ T-cell effectors contribute to protective recall responses is unclear. Here, we compare these effectors directly after influenza A virus infection. Both develop with similar kinetics, but 2° effectors accumulate in greater number in the infected lung and are the critical component of memory CD4+ T-cell–mediated protection against influenza A virus, independent of earlier-acting memory-cell helper functions. Phenotypic, functional, and transcriptome analyses indicate that 2° effectors share organ-specific expression patterns with 1° effectors but are more multifunctional, with more multicytokine (IFN-γ+/IL-2+/TNF+)-producing cells and contain follicular helper T-cell populations not only in the spleen and draining lymph nodes but also in the lung. In addition, they express more CD127 and NKG2A but less ICOS and Lag-3 than 1° effectors and express higher levels of several genes associated with survival and migration. Targeting two differentially expressed molecules, NKG2A and Lag-3, reveals differential regulation of 1° and 2° effector functions during pathogen challenge.

show abstract

Memory CD4 T Cells That Express CXCR5 Provide Accelerated Help to B Cells

Cited by 127 publications

References 46 publications

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

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

Targeting Antigen to Clec9A Primes Follicular Th Cell Memory Responses Capable of Robust Recall

Memory CD4⁺T-cell–mediated protection depends on secondary effectors that are distinct from and superior to primary effectors

Contact Info

Product

Resources

About

Memory CD4 T Cells That Express CXCR5 Provide Accelerated Help to B Cells

Cited by 127 publications

References 46 publications

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

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

Targeting Antigen to Clec9A Primes Follicular Th Cell Memory Responses Capable of Robust Recall

Memory CD4+T-cell–mediated protection depends on secondary effectors that are distinct from and superior to primary effectors

Contact Info

Product

Resources

About

Memory CD4⁺T-cell–mediated protection depends on secondary effectors that are distinct from and superior to primary effectors