Stimulation by Soluble CD70 Promotes Strong Primary and Secondary CD8+ Cytotoxic T Cell Responses In Vivo

Rowley, Tania F.; Al‐Shamkhani, Aymen

doi:10.4049/jimmunol.172.10.6039

Cited by 101 publications

(106 citation statements)

References 53 publications

(62 reference statements)

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“…The enhancing effect of third-party CD70 was even observed when T cells were stimulated by DC that expressed CD70 by themselves. Other studies have also shown bystander activity of CD70; application of soluble CD70 in vivo augmented CD8 T cell responses after immunization with the OVA peptide (47). It remains to be seen whether CD27 stimulatory signals in trans and cis positions relative to the TCR differ in their signaling cascades and functional outcomes.…”

Section: Discussionmentioning

confidence: 95%

Unchecked CD70 Expression on T Cells Lowers Threshold for T Cell Activation in Rheumatoid Arthritis

Lee

Yang

et al. 2007

The Journal of Immunology

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Rheumatoid arthritis (RA) is characterized by premature immune aging with accumulation of degenerate T cells deficient for CD28. Gene expression profiling of CD4+CD28− and CD4+CD28+ T cells to discover disease-promoting activities of CD28− T cells identified expression of CD70 as a most striking difference. Hence, CD70 was significantly more expressed in CD4 T cells from RA patients compared with age-matched controls (p < 0.006). The underlying mechanism was a failure to repress CD70 expression after activation-dependent induction. This defect in RA was not related to differential promoter demethylation. CD70 on bystander CD4+CD28− T cells functioned by lowering the threshold for T cell activation; admixture of CD4+CD28− T cells augmented TCR-induced responses of autologous naive CD4+CD28+ T cells, particularly of low-avidity T cells. The data support a model in which CD70 expressed on T cells causes degeneracy in T cell responses and undermines tolerance mechanisms that normally control T cell autoreactivity.

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Section: Discussionmentioning

confidence: 95%

Unchecked CD70 Expression on T Cells Lowers Threshold for T Cell Activation in Rheumatoid Arthritis

Lee

Yang

et al. 2007

The Journal of Immunology

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“…Interestingly, the requirement for 4-1BB costimulation during the primary response to influenza virus is greater during infection with a more virulent strain of virus, consistent with the higher expression of 4-1BB on activated T cells from mice bearing a higher viral load (13). Although the lack of CD27 signaling results in suboptimal CD8 T cell responses (12,(14)(15)(16)(17), deliberate triggering of CD27 by administration of soluble rCD70 (18) or through transgenic expression of CD70 on DCs (19) prevents tolerance induced by injection of a peptide Ag and allows the generation of a population of effector and memory CD8 T cells. Similarly, 4-1BB triggering was shown to prevent peptide-induced CD8 T cell tolerance (20) and augment effector and memory responses following peptide or DC immunization (21)(22)(23).…”

mentioning

confidence: 77%

Differential Impact of CD27 and 4-1BB Costimulation on Effector and Memory CD8 T Cell Generation following Peptide Immunization

Willoughby

Kerr

Rogel

et al. 2014

The Journal of Immunology

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The factors that determine differentiation of naive CD8 T cells into memory cells are not well understood. A greater understanding of how memory cells are generated will inform of ways to improve vaccination strategies. In this study, we analyzed the CD8 T cell response elicited by two experimental vaccines comprising a peptide/protein Ag and an agonist that delivers a costimulatory signal via CD27 or 4-1BB. Both agonists increased expansion of Ag-specific CD8 T cells compared with Ag alone. However, their capacity to stimulate differentiation into effector and memory cells differed. CD27 agonists promoted increased expression of perforin and the generation of short-lived memory cells, whereas stimulation with 4-1BB agonists favored generation of stable memory. The memory-promoting effects of 4-1BB were independent of CD4 T cells and were the result of programing within the first 2 d of priming. Consistent with this conclusion, CD27 and 4-1BB–stimulated CD8 T cells expressed disparate amounts of IL-2, IFN-γ, CD25, CD71, and Gp49b as early as 3 d after in vivo activation. In addition, memory CD8 T cells, generated through priming with CD27 agonists, proliferated more extensively than did 4-1BB–generated memory cells, but these cells failed to persist. These data demonstrate a previously unanticipated link between the rates of homeostatic proliferation and memory cell attrition. Our study highlights a role for these receptors in skewing CD8 T cell differentiation into effector and memory cells and provides an approach to optimize vaccines that elicit CD8 T cell responses.

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“…As OX40 ligand is expressed by B cells, the CXCR5 + CD8 T cells could be positively regulated by B cells in the follicle via this receptor pair [45]. One could also speculate that CD8 T cells may use CD27-CD70-mediated interaction with B cells to increase effector CD8 T cell pool size and increase IFN-c production [46][47][48]. The possible functional consequences for the CD8 T cells from interacting with B cells and CD4 T cells in the follicle warrant further study.…”

Section: Discussionmentioning

confidence: 99%

CXCR5⁺ CCR7^– CD8 T cells are early effector memory cells that infiltrate tonsil B cell follicles

et al. 2007

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Naive and central memory CD8 T cells use CCR7 to recirculate through T cell zones of secondary lymphoid organs where they can encounter antigen. Here we describe a subset of human CD8 T cells expressing CXCR5 which enables homing in response to CXCL13 produced within B cell follicles. CXCR5 + CD8 T cells were found in tonsil B cell follicles, and isolated cells migrated towards CXCL13 in vitro. They expressed CD27, CD28, CD45RO, CD69, and were CD7 low , and produced IFN-c and granzyme A but lacked perforin, a functional profile suggesting that these cells are early effector memory cells in the context of contemporary T cell differentiation models. Receptors important in the interaction with B cells, including CD70, OX40 and ICOS, were induced upon activation, and CXCR5 + CD8 T cells could to some extent support survival and IgG production in tonsil B cells. Furthermore, CXCR5 + CD8 T cells expressed CCR5 but no CCR7, suggesting a migration pattern distinct from that of follicular CD4 T cells. The finding that a subset of early effector memory CD8 T cells use CXCR5 to locate to B cell follicles indicates that MHC class I-restricted CD8 T cells are part of the follicular T cell population. IntroductionCD8 T cells are lymphocytes of the adaptive immune system which recognize viral and bacterial peptides presented by MHC class I molecules and are indispensable in the control of many intracellular infections [1]. When appropriately stimulated by antigen presented by dendritic cells (DC) in secondary lymphoid tissues, they proliferate vigorously, become effector cells, and upon resolution of infection a small population of antigen-specific CD8 T cells are maintained as long-lived memory cells [2][3][4]. A primary effector mechanism of CD8 T cells is the killing of infected cells via the targeted release of the lytic effector molecules perforin and granzymes, and via expression of death receptors. However, there is significant functional heterogeneity in CD8 T cells and they are also efficient in producing anti-viral and pro-inflammatory cytokines [5][6][7][8]. The effector mechanisms used may depend on the pathogen and on the type of cell or tissue that is infected [8].CD8 T cell responses involve the differentiation of naive T cells into distinct types of effector and memory cells [2, 3,9]. One approach to analyse a T cell response is to examine the expression of receptors that mediate homing of T cells, such as CD62L, which binds to glycosylation-dependent cell adhesion molecule 1 on [4,20,21]. CXCR5 is a chemokine receptor which is expressed on all B cells and on specialized subsets of DC and T cells [22]. It has only one known ligand, the chemokine CXCL13, mainly produced by stromal cells and follicular DC within B cell follicles [23][24][25]. CXCR5 + CD4 T cells, known as follicular homing T helper cells, are found in B cell follicles and contribute to the generation of effective humoral immune responses by supporting antibody production and isotype class switching [26,27]. However, some of the processes and mec...

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Stimulation by Soluble CD70 Promotes Strong Primary and Secondary CD8+ Cytotoxic T Cell Responses In Vivo

Cited by 101 publications

References 53 publications

Unchecked CD70 Expression on T Cells Lowers Threshold for T Cell Activation in Rheumatoid Arthritis

Unchecked CD70 Expression on T Cells Lowers Threshold for T Cell Activation in Rheumatoid Arthritis

Differential Impact of CD27 and 4-1BB Costimulation on Effector and Memory CD8 T Cell Generation following Peptide Immunization

CXCR5⁺ CCR7^– CD8 T cells are early effector memory cells that infiltrate tonsil B cell follicles

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Stimulation by Soluble CD70 Promotes Strong Primary and Secondary CD8+ Cytotoxic T Cell Responses In Vivo

Cited by 101 publications

References 53 publications

Unchecked CD70 Expression on T Cells Lowers Threshold for T Cell Activation in Rheumatoid Arthritis

Unchecked CD70 Expression on T Cells Lowers Threshold for T Cell Activation in Rheumatoid Arthritis

Differential Impact of CD27 and 4-1BB Costimulation on Effector and Memory CD8 T Cell Generation following Peptide Immunization

CXCR5+ CCR7– CD8 T cells are early effector memory cells that infiltrate tonsil B cell follicles

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CXCR5⁺ CCR7^– CD8 T cells are early effector memory cells that infiltrate tonsil B cell follicles