Dendritic cells capable of stimulating T cells in germinal centres

Grouard, Géraldine; Durand, Isabella; Filgueira, Luis; Banchereau, Jacques; Liu, Yongjun

doi:10.1038/384364a0

Cited by 277 publications

(174 citation statements)

References 27 publications

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“…In this way, we artificially relocated T cell zone-localized cells into a GC-like microenvironment. First, in agreement with previous results (43), GC B cells were poor in eliciting proliferation of naive T cells from peripheral blood. However, MLR performed with GC B cells and CD4 ϩ CXCR5 dim T cells isolated from tonsils obtained from two different donors displayed substantial proliferation where the T cells gradually outnumbered the B cells (data not shown).…”

Section: T Cells With a Cxcr5 Dim Phenotype Spontaneously Develop Intsupporting

confidence: 80%

Germinal Centers Regulate Human Th2 Development

Johansson‐Lindbom

Ingvarsson

Borrebaeck

2003

The Journal of Immunology

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In the present study we demonstrate that all CD4+ T cells in human tonsil expressing the Th2-selective receptor chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) also 1) express high levels of CXCR5, and 2) display a transitional CD45RA/RO phenotype and consistently do not produce significant amounts of cytokines when immediately analyzed ex vivo. Hence, they represent precursors of Th2 effector cells, a conclusion confirmed by their robust production of IL-4, IL-5, and IL-13, but not IFN-γ, after in vitro activation. CD4+ T cells, which express only intermediate levels of CXCR5, instead develop into IFN-γ-producing cells under identical culture conditions, thus establishing a correlation between relative levels of CXCR5 expression and the acquired cytokine profile. Because CXCR5 is critically involved in follicular localization, the results suggest that these CRTH2+ Th2 cells preferentially develop their cytokine-producing phenotype within germinal centers (GCs), whereas extrafollicular differentiation instead promotes Th1 development. In support for this proposal, we show that T cells with an intermediate expression of CXCR5 can be forced to also produce IL-4 and IL-13 if cultured with allogenic GC B cells. Finally, we demonstrate that the previously described CD57+ GC T cells also express high levels of CXCR5 but instead of comprising a Th2 precursor, they represent anergized T cells. Taken together, these data suggest that GCs and B cells regulate CD4+ T cell differentiation in a finely tuned fashion, either by promoting differentiation of Th2 cells, which apparently leave the lymphoid tissue before evolving a cytokine-producing phenotype, or by furnishing T cell unresponsiveness.

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Section: T Cells With a Cxcr5 Dim Phenotype Spontaneously Develop Intsupporting

confidence: 80%

Germinal Centers Regulate Human Th2 Development

Johansson‐Lindbom

Ingvarsson

Borrebaeck

2003

The Journal of Immunology

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“…Our new methodology has the advantage of avoiding potential problems of antigenic changes associated with in vitro culture 19 plus the biases induced by positive selection. This combined with a very extensive phenotypic analysis established that the apparent heterogeneity in markers noted in these other studies 16,18 could be extended into a more defined set of five DC subsets.…”

Section: Discussionmentioning

confidence: 99%

“…The previously described GCDCs were isolated based on a CD11c ϩ CD4 ϩ lin Ϫ cell phenotype 18 but, as outlined in this study, this phenotype is common to three distinct DC subsets located in both the T cell areas and germinal centers, one of which expresses CD13. This fact, plus the observation that CD13 can be induced on a subpopulation of tonsil DCs after culture (data not shown), could explain the heterogeneous expression of CD13 originally reported on GCDCs.…”

Section: Discussionmentioning

confidence: 99%

“…[7][8][9][10]14 Three tonsil DC subsets consisting of GCDCs, 18 plasmacytoid DCs, 17 and IDCs 16 have been described previously. Our new methodology has the advantage of avoiding potential problems of antigenic changes associated with in vitro culture 19 plus the biases induced by positive selection.…”

Section: Discussionmentioning

confidence: 99%

“…15 Three tonsil DC subsets have been identified: interdigitating DCs (IDCs), 16 plasmacytoid DCs, 17 and germinal center DCs (GCDCs). 18 These DC subsets were isolated after a period of in vitro culture, which is likely to alter cell phenotype and morphology. 19 They were also positively selected from lin Ϫ cells based on their expression of the CD4, CD11c, or CD40 antigens, which would exclude any DC subsets lacking these antigens and would incorporate all DC subsets expressing those antigens into one population.…”

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confidence: 99%

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Phenotypic Characterization of Five Dendritic Cell Subsets in Human Tonsils

Summers

Hock

McKenzie

et al. 2001

The American Journal of Pathology

167

121

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Dendritic cells (DCs) have a central role in the initiation and regulation of immune responses in both lymphoid and nonlymphoid tissues. They share a number of common features, notably MHC class II expression, in combination with an absence of the lineage-specific markers CD3, CD14, CD16, and CD19 (lin Ϫ ). [1][2][3] There is however considerable intra-and intertissue variation in the phenotype, morphology, function, and tissue localization of different DC populations. [1][2][3][4][5][6][7] After the identification of distinct myeloid DC and lymphoid DC subsets in mice 3 there has been increasing interest in the characterization of human DC subsets. These have been categorized on the basis of differential expression of myeloid and lymphoid lineage-associated markers, as well as their responsiveness to maturation or differentiation stimuli. 8 -13 There is evidence that myeloid DCs and lymphoid DCs direct immunogenic and tolerogenic responses, respectively. 13 It is unclear whether human DC subsets represent distinct cell lineages 10,12 or differing maturation states. 9,14 As a result, the ontogeny and interrelationship of human DC subsets requires further investigation.Tonsils have been used as a readily available source of lymphoid tissue to characterize human DCs. 15 Three tonsil DC subsets have been identified: interdigitating DCs (IDCs), 16 plasmacytoid DCs, 17 and germinal center DCs (GCDCs). 18 These DC subsets were isolated after a period of in vitro culture, which is likely to alter cell phenotype and morphology. 19 They were also positively selected from lin Ϫ cells based on their expression of the CD4, CD11c, or CD40 antigens, which would exclude any DC subsets lacking these antigens and would incorporate all DC subsets expressing those antigens into one population. The observation that both IDCs and GCDCs were heterogeneous with regard to CD11c, CD83, HLA-DR, and CD13 intensity raised the possibility that these tonsil DC populations might contain additional subsets. This is the first study to analyze the composition of tonsil DC subsets within the entire lin Ϫ HLA-DR ϩ DC population isolated using a new method that maintains the cells at 4°C to minimize changes in cellular differentiation/activation induced by the isolation procedure. We report the presence of five distinct DC subsets within human tonsils. The phenotype of each tonsil DC subset was analyzed by threecolor flow cytometry and two-color immunohistochemistry using an extensive panel of antigens relevant to DC lineage, activation state, and function. Materials and Methods Patients and SamplesAfter approval by the Canterbury Ethics Committee and appropriate informed consent, tonsils were obtained from 68 patients undergoing routine tonsillectomies, which were excised in a noninflamed state. They were trans-

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Cloning of two members of the SIRPα family of protein tyrosine phosphatase binding proteins in cattle that are expressed on monocytes and a subpopulation of dendritic cells and which mediate binding to CD4 T cells

1998

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Recent experimental studies have greatly clarified the function of cell surface molecules in the induction and modulation of T cell responses by antigen-presenting cells (APC). However, the differences in ability to stimulate T cells evident for different types and subpopulations of the same APC, such as dendritic cell subsets, is less well understood. This report details an investigation of an antigen expressed on monocytes that is also expressed on a subset of cattle afferent lymph veiled cells (ALVC). A cDNA library derived from cattle monocytes was screened with monoclonal antibodies (mAb) for expression in COS-7 cells. Using separate mAb for screening, two cDNA were cloned, the sequences of which showed a single long open reading frame encoding a predicted type I glycoprotein of 506 amino acids that contained three immunoglobulin superfamily domains and a long 112-amino acid cytoplasmic tail. We have termed this antigen MyD-1, reflecting its myeloid and dendritic cell distribution. Analysis of the EMBL database revealed that the molecule is a member of the recently described family of signal regulatory proteins (SIRP). The outeremost Ig domain was of the adhesion/receptor I-type, suggesting that MyD-1 might bind to a ligand on another cell. Evidence for this was subsequently obtained by demonstrating that COS-7 cells transfected with MyD-1 cDNA bound CD4 T cells and this binding was blocked by specific mAb. The potential importance of this interaction was supported by the finding that the proliferation of resting memory CD4 T cells to ovalbumin-pulsed monocytes was significantly reduced in the presence of mAb to MyD-1. A role for the molecule in the modulation of the monocyte/dendritic APC response is also predicted from the existence of multiple potential tyrosine phosphorylation sites in the cytoplasmic domain, including the presence of an immunoreceptor tyrosine-based inhibitory motif (ITIM) and the observation that the SIRP alpha family members have been shown to bind to SHP-1 and SHP-2. Together these data indicate a possible functional importance for MyD-1 in the regulation of monocyte and dendritic cell function.

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Dendritic cells capable of stimulating T cells in germinal centres

Cited by 277 publications

References 27 publications

Germinal Centers Regulate Human Th2 Development

Germinal Centers Regulate Human Th2 Development

Phenotypic Characterization of Five Dendritic Cell Subsets in Human Tonsils

Cloning of two members of the SIRPα family of protein tyrosine phosphatase binding proteins in cattle that are expressed on monocytes and a subpopulation of dendritic cells and which mediate binding to CD4 T cells

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