Regional Phenotypic Specialization of Intraepithelial Lymphocytes in the Rat Intestine Does Not Depend on Microbial Colonization

Helgeland, Lars; Vaage, John T.; Rolstad, Bent; Halstensen, Trond S.; Midtvedt, Tore; Brandtzæg, Per

doi:10.1046/j.1365-3083.1997.d01-133.x

Cited by 40 publications

(42 citation statements)

References 38 publications

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“…Many IEL were CD4/CD8 double negative ( Fig. 1), in agreement with our previous immunohistochemical [8] and flow cytometric [5] findings in the same strain of GF and CV rats. These CD4/CD8 double-negative cells expressed a 'null' phenotype, i.e.…”

Section: Microbial Colonization Alters the Phenotypic Composition Of supporting

confidence: 92%

“…Conversely, CD4 + IEL were lacking in GF rats, but significant numbers of CD4 SP and CD4/CD8a DP IEL were found in CV rats. Thus, these cells are a useful indicator of a successful CV status [4,5,8]. Many IEL were CD4/CD8 double negative ( Fig.…”

Section: Microbial Colonization Alters the Phenotypic Composition Of mentioning

confidence: 99%

“…Unlike CD4 + IEL, CD8 SP IEL do not depend on the microflora for their development, because the latter occur in significant numbers in germ-free (GF) animals as judged by immunohistochemistry or flow cytometry [5,[7][8][9]. In rats, colonization of the jejunal epithelium occurs in sequence with cd and ab T lymphocytes (both CD8ab + ) perinatally, and this takes place prior to weaning [10], that is before the establishment of a complete intestinal flora [11,12].…”

Section: Introductionmentioning

confidence: 99%

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Microbial colonization induces oligoclonal expansions of intraepithelial CD8 T cells in the gut

et al. 2004

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Two populations of CD8+ IEL generally express restricted, but apparently random and nonoverlapping TCR repertoires. Previous studies in mice suggested that this could be explained by a dual origin of CD8 + IEL, i.e. that CD8ab + IEL derive from a few peripheral CD8 + T cell lymphoblasts stimulated by microbial antigens in gut-associated lymphoid tissue, whereas CD8aa + IEL descend from an inefficient intestinal maturation pathway. We show here that the gut mucosa, instead, becomes seeded with surprisingly broad and generally nonoverlapping CD8 IEL repertoires and that oligoclonality is induced locally after microbial colonization. In germ-free (GF) rats, both CD8ab + and CD8aa + IEL displayed surprisingly diverse TCR Vb repertoires, although b-chain diversity tended to be somewhat restricted in the CD8aa + subset. CDR3 length displays in individual Vb-Cb and Vb-Jb combinations generally revealed polyclonal distributions over 6-11 different lengths, similar to CD8 + lymph node T cells, and CDR3b sequencing provided further documentation of repertoire diversity. By contrast, in ex-GF rats colonized with normal commensal microflora, both CD8ab + and CD8aa + IEL displayed oligoclonal CDR3 length distributions for most of the Vb genes analyzed. Our data suggest that microbial colonization induces apparently random clonal expansions of CD8ab + and CD8aa + IEL locally in the gut.

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Section: Microbial Colonization Alters the Phenotypic Composition Of supporting

confidence: 92%

Section: Microbial Colonization Alters the Phenotypic Composition Of mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Microbial colonization induces oligoclonal expansions of intraepithelial CD8 T cells in the gut

et al. 2004

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“…Bacteria might be necessary to stimulate epithelial cells to produce growth factors for IEL: nutritional antigens and microbial factors do not seem to be sufficient. However, in a recent study in rats it was demonstrated that the subset composition in germ-free and conventional animals did not differ, although the numbers of IEL were lower in germ-free animals [32]. The local proliferation of IEL in the pig is of major interest as it further documents the heterogeneity between species: Halstensen & Brandtzaeg [10] did not see any IEL in normal human intestine in the cell cycle (Ki67 þ ) but about 13% positive cells in coeliac patients.…”

Section: Discussionmentioning

confidence: 88%

The Influence of Age and Breeding Conditions on the Number and Proliferation of Intraepithelial Lymphocytes in Pigs

1999

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The number and subset composition of intraepithelial lymphocytes (IEL) were studied in pigs in different age groups ranging from 1 day to 4.5 years. There were no major differences between the numbers of IEL in the jejunum and ileum. The postnatal increase of IEL largely depended on the breeding conditions: in germ-free animals there was a constant level, while in conventionally bred pigs the numbers increased more obviously than in specified pathogen-free (SPF) pigs. As the numbers of IEL can rise due to increased influx from other organs, decreased emigration, decreased apoptosis or local proliferation, the incorporation of the DNA precursor bromodeoxyuridine (BrdU) by IEL was studied after different labelling protocols. There were low but definite numbers of BrdU þ IEL 1 h after BrdU, indicating in-situ proliferation in conventional animals with a tendency to a higher index in the jejunum than the ileum. Repetitive labelling protocols for 14 days resulted in 12-20% BrdU þ IEL, which may be caused by local proliferation and immigration of lymphocytes produced in other lymphoid organs as documented for the pig. Future studies need to focus on the factors regulating local proliferation and the migration of IEL in different species.

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“…NKR-P1F was also expressed on a subset of conventional (CD3 + NKR-P1A − ) T cells in liver, PP, and on the majority of CD3 + IELs (Fig. 4A), of which only a fraction expressed NKR-P1A [33]. NKR-P1G was also expressed by T cells in the liver and gut.…”

mentioning

confidence: 95%

Functional characterization of a conserved pair of NKR‐P1 receptors expressed by NK cells and T lymphocytes in liver and gut

et al. 2014

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Natural killer cell receptor protein 1 (NKR-P1) molecules are C-type lectin-like receptors modulating cellular responses toward target cells expressing C-type lectin-like related (Clr) molecules. Although the function of the prototypic rat NKR-P1A receptor and its inhibitory counterpart NKR-P1B are known, little is known about NKR-P1F and NKR-P1G apart from their promiscuity for Clr ligands. Here we generated mAbs against both receptors for phenotypic and functional analyses in rat tissues. NKR-P1F induced redirected lysis and robust Ca 2+ signaling in NK cells, which were prevented by simultaneous engagement of NKR-P1G. NKR-P1G also inhibited NK-cell lysis of Clr transfectants. NKR-P1F was expressed by most NK cells and NKR-P1A + T cells in all tissues analyzed, and by many NKR-P1A − intestinal T cells, while NKR-P1G was expressed by subsets of these cells with highest prevalence in gut and liver. In the intraepithelial compartment, the proportion of NKR-P1A + and NKR-P1F + cells was high at birth and thereafter declined, while NKR-P1B + and NKR-P1G + cells increased with age. Expression levels were also modulated by cytokines, with an increase of NKR-P1B and NKR-P1G induced by inflammatory cytokines, and a reduction of NKR-P1A by TGF-β. The physiological impact of NKR-P1 receptors might thus be dependent on age, tissue, and inflammatory status.Keywords: C-type lectin-related molecules r NK-cell receptors r NKR-P1 r Rodent Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionNatural killer (NK) cells are innate lymphoid cells with the ability to eliminate virally infected cells and transformed or allogeneic cells. They produce cytokines early in the immune response, and play an important role in shaping the immune response, e.g. in the context of inflammation and transplantation. These tasks are controlled by a wide range of receptors with different functions and ligands, such as Ly49 receptors, which recognize both classical and nonclassical MHC class I molecules, as well as MHC Correspondence: Dr. Lise Kveberg e-mail: lise.kveberg@rr-research.no class I-like virally encoded ligands [1][2][3]. Another family of MHCbinding receptors is the conserved NKG2/CD94 heterodimers, which bind the nonclassical MHC molecule HLA-E in human [4], its rodent homologue Qa-1 b in the mouse [5,6] and RT.BM1 in the rat [7]. Both the Ly49 and NKG2/CD94 receptor families contain inhibitory and activating members. NKG2D is a promiscuous activating receptor, recognizing several MHC class I-related ligands frequently upregulated upon cellular stress and associated with viral infection and malignant transformation [8].The activating NK cytotoxicity receptors react with several virus-derived and endogenous ligands [9,10].One of the earliest NK-cell receptors to be characterized was the NK-cell receptor protein 1A (NKR-P1A) in the rat, which is C 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 502Lise Kveberg et al. Eur. J. Immunol. 2015. 45: 501-...

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Regional Phenotypic Specialization of Intraepithelial Lymphocytes in the Rat Intestine Does Not Depend on Microbial Colonization

Cited by 40 publications

References 38 publications

Microbial colonization induces oligoclonal expansions of intraepithelial CD8 T cells in the gut

Microbial colonization induces oligoclonal expansions of intraepithelial CD8 T cells in the gut

The Influence of Age and Breeding Conditions on the Number and Proliferation of Intraepithelial Lymphocytes in Pigs

Functional characterization of a conserved pair of NKR‐P1 receptors expressed by NK cells and T lymphocytes in liver and gut

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