Functional Subsets of Memory T Cells Identified by CCR7 Expression

Sallusto, Federica; Langenkamp, Anja; Geginat, Jens; Lanzavecchia, Antonio

doi:10.1007/978-3-642-57276-0_21

Cited by 114 publications

(115 citation statements)

References 16 publications

Supporting

Mentioning

104

Contrasting

Unclassified

Order By: Relevance

“…These results, added to those of others, suggest that protective T cell memory is not due to long-lived memory T cells but rather to frequently dividing ''activated effector T cells'' (28,29) or dividing effector memory T cells (25,27,30). Our results also indicate that ex vivo analysis of immunophenotype or IFN-␥ production so far is not predictive of immunological memory.…”

Section: Discussionsupporting

confidence: 46%

“…based on telomere shortening (21,22,25) or BrdUrd incorporation (11)(12)(13)26). Indeed, despite major losses of CD44 hi T cells in tissues where the memory T cells localize after sensitization (27), overall, up to 31% (in B6 euthymic mice) and 67% (in B6 thymectomized mice; data not shown) of the CD44 hi T cells persisted in mice with immune amnesia compared with control-sensitized mice.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Turning immunological memory into amnesia by depletion of dividing T cells

Bellier

Thomas‐Vaslin

Saron

et al. 2003

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

View full text Add to dashboard Cite

Immunological memory, defined as more efficient immune responses on antigen reexposure, can last for decades. The current paradigm is that memory is maintained by antigen-experienced ''memory T cells'' that can be long-lived quiescent or dividing. The contribution of T cell division to memory maintenance is poorly known and has important clinical implications. In this study, we directly addressed the role of dividing T cells in immunological memory maintenance by evaluating the consequences of their elimination. The specific ablation of dividing T cells was obtained by administration of ganciclovir to immune mice expressing the herpes simplex type 1 thymidine kinase suicide gene in T cells. We show that depletion of dividing T cells for 5 or 2 weeks suffices to abolish in vitro and in vivo memory responses against the male H-Y transplantation alloantigen or against lymphocytic choriomeningitis virus antigens, respectively. Similar results were obtained after the nonspecific elimination of all dividing cells by using hydroxyurea, a cytostatic toxic agent commonly used for cancer chemotherapy. This immune amnesia occurred in otherwise immunocompetent mice and despite the persistence of functional quiescent T cells displaying a ''memory'' phenotype. Thus, division of antigen-experienced T cells is an absolute requirement for immunological memory maintenance and the current concept of memory T cells is challenged.I mmunological memory is one of the main features of adaptative immunity. It is characterized by a more rapid and intense immune response on reexposure to an immunogen. In responses against pathogens, immunological memory can translate into infection protection that can last for decades. The population dynamics of lymphocytes that ensures long-term memory maintenance in vivo and the physiological consequences of this dynamics are poorly understood. In particular, the respective contributions of long-lived quiescent vs. dividing T cells for immunological memory maintenance remain to be investigated.The current paradigm is that ''memory T cells'' support immunological memory. Tentative identification of these cells has been based on cell surface markers whose high ( hi ) or low ( lo ) expression levels are modulated on activation (1, 2). Likewise in mice, T cells are commonly subdivided into naive (CD44 lo -CD45RB hi -CD62L hi ), effector (CD44 hi -CD45RB lo/hi -CD62L lo ), and memory subsets (CD44 hi -CD45RB lo -CD62L lo ). However, this immunophenotypic classification is simplistic: (i) the memory T cell phenotype appears quite heterogeneous (3), different for CD4 ϩ and CD8 ϩ T cells, comprising at least two subsets referred to as ''effector memory '' and ''central memory'' T cells (4-6); (ii) phenotypic changes from naive to memory͞effector type may be a stigmata of antigen (Ag) activation rather than a hallmark of memory͞effector function; (iii) at least some of these phenotypic changes are reversible (3, 7); (iv) homeostatic proliferation can induce naive T cells to acquire the memory͞ effector phenotype...

show abstract

Section: Discussionsupporting

confidence: 46%

Section: Discussionmentioning

confidence: 99%

Turning immunological memory into amnesia by depletion of dividing T cells

Bellier

Thomas‐Vaslin

Saron

et al. 2003

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

View full text Add to dashboard Cite

show abstract

Section: Establishment Of Effector Memory Wt and Psgl-1 −/− Sjl/j T-cmentioning

confidence: 62%

“…The chemokine CCL19 is constitutively expressed on BBB endothelium and was proposed to mediate infiltration of chemokine (C-C motif) receptor 7 (CCR7) + T cells into the CNS [19,20]. Both our WT and PSGL-1 −/− T-cell lines did not bind a CCL19 Ig fusion protein, confirming that our T cells were CCR7 neg effector/memory T cells [21].Differentiation of CD4 + T helper cells into either Th1 or Th17 cells was shown to influence the molecular mechanisms these T-cell subsets use to enter the CNS during EAE [22]. While Th1 cells critically rely on α4-integrins, Th17 cells can cross the brain barriers in an α4-integrin-independent manner and enter the CNS [22,23].…”

mentioning

confidence: 64%

PSGL‐1 and E/P‐selectins are essential for T‐cell rolling in inflamed CNS microvessels but dispensable for initiation of EAE

et al. 2014

View full text Add to dashboard Cite

T-cell migration across the blood-brain barrier is a crucial step in the pathogenesis of EAE, an animal model for MS. Live cell imaging studies demonstrated that P-selectin glycoprotein ligand-1 (PSGL-1) and its endothelial ligands E-and P-selectin mediate the initial rolling of T cells in brain vessels during EAE. As functional absence of PSGL-1 or E/P-selectins does not result in ameliorated EAE, we speculated that T-cell entry into the spinal cord is independent of PSGL-1 and E/P-selectin. Performing intravital microscopy, we observed the interaction of WT or PSGL-1 −/− proteolipid protein-specific T cells in inflamed spinal cord microvessels of WT or E/P-selectin −/− SJL/J mice during EAE. T-cell rolling but not T-cell capture was completely abrogated in the absence of either PSGL-1 or E-and P-selectin, resulting in a significantly reduced number of T cells able to firmly adhere in the inflamed spinal cord microvessels, but did not lead to reduced T-cell invasion into the CNS parenchyma. Thus, PSGL-1 interaction with E/P-selectin is essential for T-cell rolling in inflamed spinal cord microvessels during EAE. Taken together with previous observations, our findings show that T-cell rolling is not required for successful T-cell entry into the CNS and initiation of EAE.Keywords: Blood-brain barrier r Experimental autoimmune encephalomyelitis r P-selectin r P-selectin glycoprotein ligand-1 r T-cell rolling Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionIn MS, and in its animal model, EAE, neuro-Ag-specific CD4 + (where CD is cluster of differentiation) T cells breach the bloodbrain barrier (BBB) and gain access to the CNS, where they cause inflammation, demyelination, and BBB breakdown leading to the clinical manifestation of these diseases. T-cell migration across the BBB is a multi-step process mediated by the sequential interaction of different adhesion and/or signaling molecules on the T cells and Correspondence: Prof. Britta Engelhardt e-mail: bengel@tki.unibe.ch the highly specialized endothelium of the BBB [1]. The discovery that α4β1-integrin plays a critical role in T-cell trafficking across the BBB during EAE has led to the development of a humanized monoclonal anti-α4-integrin Ab (natalizumab) for the treatment of MS [2].In vivo live cell imaging studies have provided direct evidence that the multistep extravasation of encephalitogenic T cells across the spinal cord microvasculature during initiation of EAE is unique [3]. Initiation of T-cell interaction with the spinal cord microvascular endothelium takes place in the absence of rolling and is rather mediated by α4-integrin-mediated G-protein-independent capture and subsequent G-protein-dependent arrest of the T cells in spinal cord microvessels [3]. Once neuroinflammation iswww.eji-journal.eu 2288 Karthik Sathiyanadan et al. Eur. J. Immunol. 2014. 44: 2287-2294 ongoing, it is mostly T-cell rolling with a few alternative capture events also detected, which characterize th...

show abstract

“…The multimer staining results are suggestive of a CD8 þ immune response mounted by the patients, so we sought to define this further by co-staining the cells using the T cell memory phenotype markers CD45 RA and RO, 30,31 and CCR7, [32][33][34] Effector and central memory T cells express the RO isoform of the CD45 molecule, whereas naïve cells express the RA isoform. In addition, only central memory and naïve cells express CCR7.…”

Section: Peptide-pulsed Hla-a*0201 Target Tumor Cells Can Induce Ifn-mentioning

confidence: 99%

T cells reactive with HLA‐A*0201 peptides from the histone demethylase JARID1B are found in the circulation of breast cancer patients

Coleman

Correa

Cooper

et al. 2011

Intl Journal of Cancer

View full text Add to dashboard Cite

The nuclear protein PLU-1/JARID1B/KDM5 is widely expressed in breast cancers while showing highly restricted expression in normal adult tissues. To investigate whether JARID1B is a potential target antigen for immunotherapy of breast cancer, we have analyzed the responses of CD8 1 T cells to JARID1B HLA-A*0201 peptides in vitro and used peptide multimers to detect the presence of JARID1B reactive T cells in the circulation of breast cancer patients. Peptides were selected using two webbased algorithms: criteria for inclusion being a high score in both prediction algorithms, and nonhomology with retinoblastoma binding protein-2 (RBP2/JARID1A/KDM5A). A 65-peptide panel was selected and assayed for binding strength by competition assay to obtain the IC 50 . The immunogenicity in vitro of these peptides was assessed by T cell stimulation experiments, using autologous dendritic cells as APCs in the first rounds followed by autologous lymphoblasts. Fourteen of the peptides assayed produced cultures having >2% of the CD8 1 cells being IFN-c 1 after 3-6 rounds of stimulation. An HLA-A*0201 cell line could activate the specific T cells if pulsed with peptide, but endogenous peptide levels were insufficient for activation. Nevertheless, multimer staining of circulating T cells from breast cancer patients showed a significantly higher percentage of multimer positive CD8 1 T cells, as compared to healthy adults for two of three JARID1B epitopes tested. One of these, peptide 73 (QLYALPCVL), was analyzed for memory phenotype, and found to have a significantly higher proportion of central memory T cells than the control group, demonstrating a previous exposure to the peptide.

show abstract

Functional Subsets of Memory T Cells Identified by CCR7 Expression

Cited by 114 publications

References 16 publications

Turning immunological memory into amnesia by depletion of dividing T cells

Turning immunological memory into amnesia by depletion of dividing T cells

PSGL‐1 and E/P‐selectins are essential for T‐cell rolling in inflamed CNS microvessels but dispensable for initiation of EAE

T cells reactive with HLA‐A*0201 peptides from the histone demethylase JARID1B are found in the circulation of breast cancer patients

Contact Info

Product

Resources

About