L-selectin-negative CCR7− effector and memory CD8+ T cells enter reactive lymph nodes and kill dendritic cells

Guarda, Greta; Hons, Miroslav; Soriano, Silvia F.; Huang, Alex Y.; Polley, Rosalind; Martín-Fontecha, Alfonso; Stein, Jens V; Germain, Ronald N.; Lanzavecchia, Antonio; Sallusto, Federica

doi:10.1038/ni1469

Cited by 190 publications

(232 citation statements)

References 54 publications

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“…The stochastic nature of interaction between immune cells during immune responses can predict the generation of effector CD8 T cells with phenotypes similar to the one described in this manuscript (31,35). This will be especially true for the secondary response where rapidly reactivated Ag-specific memory CD8 T cells would quickly deplete Ag-carrying APCs, creating a condition permissive for brief stimulation of naive CD8 T cells (36). This scenario would allow naive CD8 T cells involved in an immune response to bypass full effector differentiation and transit directly into the memory stage (37), thus preventing excessive generation of full-blown effector CD8 T cells while preserving efficient recruitment into the memory pool.…”

Section: Discussionmentioning

confidence: 99%

Brief Antigenic Stimulation Generates Effector CD8 T Cells with Low Cytotoxic Activity and High IL-2 Production

Usharauli

Kamala

2008

The Journal of Immunology

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It is currently believed that a brief antigenic stimulation is sufficient to induce CD8 T cells to complete their differentiation program, become effector T cells, and subsequently generate memory. Because this concept was derived from studies in which only a single effector function was analyzed (either IFN-γ production or target cell lysis), we wondered whether monitoring for multiple effector functions might reveal novel characteristics of effector CD8 T cells elicited by brief or prolonged Ag exposure. Using an in vitro system to generate effector T cells and an in vivo adoptive transfer model to track donor CD8 T cells, we found that the differentiation programs acquired by CD8 T cells after brief or prolonged antigenic stimulation were different. Although the frequencies of IFN-γ and TNF-α producers were comparable for both effector CD8 T cell populations, there were major differences in cytotoxic potential and IL-2 production. Whereas prolonged (>24 h) Ag exposure stimulated effector CD8 T cells with high cytotoxic activity and low IL-2 production, brief (<24 h) stimulation generated effector CD8 T cells with low cytotoxic activity and high IL-2 production. The latter effector T cells rapidly converted into central memory-like CD8 T cells, exhibited long-term survival in adoptively transferred hosts, and gave robust recall responses upon Ag challenge. These data suggest that not all functions of effector CD8 T cells are equally inherited after brief or prolonged antigenic stimulation.

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Section: Discussionmentioning

confidence: 99%

Brief Antigenic Stimulation Generates Effector CD8 T Cells with Low Cytotoxic Activity and High IL-2 Production

Usharauli

Kamala

2008

The Journal of Immunology

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“…Potentially, memory cells might also use similar mechanisms to control boosting responses. Recently, it has been shown that effector and effector memory cells, which are normally excluded from resting lymph nodes, can enter reactive (inflamed) lymph nodes in a CXCR3-dependent manner and kill DCs (42). Additionally, memory CD8 ϩ T cells might clear Ag in the periphery, preventing it from being cross-presented in the lymphoid tissues.…”

Section: Discussionmentioning

confidence: 99%

Memory CD8+ T Cell Responses Expand When Antigen Presentation Overcomes T Cell Self-Regulation

Cockburn

Chakravarty

Overstreet

et al. 2008

The Journal of Immunology

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Antimicrobial memory CD8+ T cell responses are not readily expanded by either repeated infections or immunizations. This is a major obstacle to the development of T cell vaccines. Prime-boost immunization with heterologous microbes sharing the same CD8+ epitope can induce a large expansion of the CD8+ response; however, different vectors vary greatly in their ability to boost for reasons that are poorly understood. To investigate how efficient memory T cell expansion can occur, we evaluated immune regulatory events and Ag presentation after secondary immunization with strong and weak boosting vectors. We found that dendritic cells were essential for T cell boosting and that Ag presentation by these cells was regulated by cognate memory CD8+ T cells. When weak boosting vectors were used for secondary immunization, pre-established CD8+ T cells were able to effectively curtail Ag presentation, resulting in limited CD8+ T cell expansion. In contrast, a strong boosting vector, vaccinia virus, induced highly efficient Ag presentation that overcame regulation by cognate T cells and induced large numbers of memory CD8+ T cells to expand. Thus, efficient targeting of Ag to dendritic cells in the face of cognate immunity is an important requirement for T cell expansion.

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“…Gene and protein expression analysis showed that although these cells were located in the LNs, γδ Trm failed to express CD62L and CCR7, but expressed CD69, CXCR3, and CXCR6. The chemokine receptor CXCR3 has previously been implicated in mediating CCR7-independent homing of activated CD8 T cells to reactive LNs (26). Because γδ Trm cells did not express the typical LN homing receptors, the expression of CXCR3 likely allowed these cells to migrate to and remain in the LNs following infection.…”

Section: Discussionmentioning

confidence: 99%

IL-17A–producing resident memory γδ T cells orchestrate the innate immune response to secondary oral Listeria monocytogenes infection

Romagnoli

Sheridan

Pham

et al. 2016

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

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Memory γδ T cells are important for the clearance of Listeria monocytogenes infection in the intestinal mucosa. However, the mechanisms by which memory γδ T cells provide protection against secondary oral infection are poorly understood. Here we used a recombinant strain of L. monocytogenes that efficiently invades the intestinal epithelium to show that Vγ4 + memory γδ T cells represent a resident memory (Trm) population in the mesenteric lymph nodes (MLNs). The γδ Trm exhibited a remarkably static pattern of migration that radically changed following secondary oral L. monocytogenes infection. The γδ Trms produced IL-17A early after rechallenge and formed organized clusters with myeloid cells surrounding L. monocytogenes replication foci only after a secondary oral infection. Antibody blocking studies showed that in addition to IL-17A, the chemokine receptor C-X-C chemokine receptor 3 (CXCR3) is also important to enable the local redistribution of γδ Trm cells and myeloid cells specifically near the sites of L. monocytogenes replication within the MLN to restrict bacterial growth and spread. Our findings support a role for γδ Trms in orchestrating protective immune responses against intestinal pathogens.

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L-selectin-negative CCR7− effector and memory CD8+ T cells enter reactive lymph nodes and kill dendritic cells

Cited by 190 publications

References 54 publications

Brief Antigenic Stimulation Generates Effector CD8 T Cells with Low Cytotoxic Activity and High IL-2 Production

Brief Antigenic Stimulation Generates Effector CD8 T Cells with Low Cytotoxic Activity and High IL-2 Production

Memory CD8+ T Cell Responses Expand When Antigen Presentation Overcomes T Cell Self-Regulation

IL-17A–producing resident memory γδ T cells orchestrate the innate immune response to secondary oral Listeria monocytogenes infection

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