CD4+CD8+ and CD8α+β- T lymphocytes in human small intestinal lamina propria

Abuzakouk, Mohamed; Carton, Janet; Feighery, Conleth; O’Donoghue, Diarmuid; Weir, Donald G.; O’Farrelly, Cliona

doi:10.1097/00042737-199804000-00009

Cited by 28 publications

(18 citation statements)

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“…Another indication that the reconstitution of the gut in BLT mice is indeed reflective of the human gut is the presence of CD8 single positive T cells in the lamina propria that expressed both the CD8α and CD8β chains which is in contrast with the exclusive expression of the CD8α chain in the double positive T cells also found in the lamina propria (Sun et al, 2007). All of these observations are fully consistent with what has been described for human gut (Abuzakouk et al, 1998; Carton et al, 2004). …”

Section: Early Descriptions Of Gut Reconstitution In Humanized Micesupporting

confidence: 92%

The use of BLT humanized mice to investigate the immune reconstitution of the gastrointestinal tract

Wahl

García

2014

Journal of Immunological Methods

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The gastrointestinal (GI) track represents an important battlefield where pathogens first try to gain entry into a host. It is also a universe where highly diverse and ever changing inhabitants co-exist in an exceptional equilibrium without parallel in any other organ system of the body. The gut as an organ has its own well-developed and fully functional immune organization that is similar and yet different in many important ways to the rest of the immune system. Both a compromised and an overactive immune system in the gut can have dire and severe consequences to human health. It has therefore been of great interest to develop animal models that recapitulate key aspects of the human condition to better understand the interplay of the host immune system with its friends and its foes. However, reconstitution of the GI tract in humanized mice has been difficult and highly variable in different systems. A better molecular understanding of the development of the gut immune system in mice has provided critical cues that have been recently used to develop novel humanized mouse models that fully recapitulate the genesis and key functions of the gut immune system of humans. Of particular interest is the presence of human gut-associated lymphoid tissue (GALT) aggregates in the gut of NOD/SCID BLT humanized mice that demonstrate the faithful development of bona fide human plasma cells capable of migrating to the lamina propria and producing human IgA1 and IgA2.

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Section: Early Descriptions Of Gut Reconstitution In Humanized Micesupporting

confidence: 92%

The use of BLT humanized mice to investigate the immune reconstitution of the gastrointestinal tract

Wahl

García

2014

Journal of Immunological Methods

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“…The present study revealed a relatively high percentage of NK cells during the first 2 wk of life; these cells were mostly CD8ϩ, differing from adult age, when they did not bear CD8. In fact, in adult human and mouse LP, NK cells either have not been detected or have been found in very low numbers (6,14,15). Although little is known about the presence and the phenotype of intestinal LP NK cells, this particular subset may act in the unspecific immune response needed on the first days of life, when subsets involved in adaptative immunity are not well developed.…”

Section: Discussionmentioning

confidence: 99%

“…Surprisingly, with the exception of day 1, CD8ϩ cells represented~40% of LPL during the first 2 wk of life. Thereafter, the percentage decreased to 14% at weaning (p Ͻ 0.0001, day 21 versus day 14), and this value remained in adult animals. Thus, the CD8ϩ population was the most abundant during the first half of the suckling period but not in adults.…”

Section: Cd45؉ Percentage In Lplmentioning

confidence: 93%

Neonatal Immunoglobulin Secretion and Lymphocyte Phenotype in Rat Small Intestine Lamina Propria

et al. 2005

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We characterized the lymphocyte phenotype and the ability to produce Ig by lamina propria (LP) cells from rat ileum throughout the suckling period. In the first week after birth, Ͻ10% of LP lymphocytes were B cells, but at weaning, this figure rose to Ͼ30% as found in the adult. These B cells did not bear surface IgA (sIgAϪ). However, the number of sIgAϩ, which may correspond to B blast cells because they were outside lymphocyte cytometer gate, increased. In LP, IgM-secreting cells (SC) appeared during the second week of life, and IgA-SC were detected later but at a lower number. Regarding LP T cells, CD8ϩ cells were more abundant than CD4ϩ cells along the first 2 postnatal weeks, and CD3ϩCD8␣␣ϩTCR␣␤ϩCD5-CD25Ϫ was their predominating phenotype. In this 2-wk period, between 8 and 20% of LP were natural killer cells. LP CD4ϩ lymphocytes in neonatal rats showed increasing co-expression of TCR␣␤, whereas the co-expression of CD90 decreased and the CD4ϩCD25ϩ cell percentage did not achieve adult values. In conclusion, in the first 2 wk of the rat life, the gut LP immune system shows abundant CD8␣␣ϩ cells, including NK cells. Thereafter, LP B cells increase dramatically and Ig-SC appear, with IgM-SC being more abundant than IgA-SC. CD4ϩ LP lymphocytes acquire a mature phenotype and adult proportions later after weaning. The mucosal surface of the small intestine is constantly exposed to a large variety of foreign antigenic materials, such as dietary macromolecules, food proteins, and autochthonous microbiota, with the resulting antigenic stimulation (1). The intestinal mucosa contains gut-associated lymphoid tissue (GALT), the largest immunologic tissue in the body, which deals with these luminal antigens. Anatomically, GALT consists of organized lymphoid structures and diffuse populations of cells. Organized GALT comprises Peyer's patches, isolated follicles, and mesenteric lymph nodes. Diffuse GALT consists of two distinct populations above and below the basement membrane: the intraepithelial lymphocytes and lamina propria (LP) mononuclear cells, including lamina propria lymphocytes (LPL). Both diffuse compartments contain mature effector T lymphocytes, and the LP compartment also contains Igproducing plasma cells (2). The intestinal immune response is primarily characterized by the production of secretory IgA by plasma cells, which predominate in human intestinal LP and represent~80% of all Ig-producing cells in the body (3,4).In humans, LP contains T CD4ϩ and T CD8ϩ lymphocytes in a similar proportion to peripheral blood, and Ͼ95% of LP T cells express the antigenic receptor ␣␤ (2,5). LP CD8ϩ T cells account for 30 -40% of LP T cells, which include cytolytic effector cells (6). Both CD4ϩ and CD8ϩ LPL express CD25 to a similar extent, with total CD25ϩ cells amounting to~15% of human intestinal LPL (5). Moreover, human LP T cells are similar to memory cells in that they have low percentages of CD45RAϩ and high percentages of CD45ROϩ and CD58ϩ cells (5). B cells in human LP are represented by a small population of sc...

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“…Rapid depletion of intestinal DP cells occurs faster and more profoundly than that of intestinal CD4 + singlepositive (SP) cells which we have previously correlated with increased levels of CCR5 expression on the former [1]. Although DP T cells have been described in the blood and intestine of humans, nonhuman primates, swine and rodents [2][3][4][5][6][7][8][9][10][11][12], little is known regarding their function or immunophenotypic (naive versus memory status etc.) characteristics.…”

Section: Introductionmentioning

confidence: 99%

Intestinal double‐positive CD4⁺CD8⁺ T cells are highly activated memory cells with an increased capacity to produce cytokines

2006

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Peripheral blood and intestinal CD4 + CD8 + double-positive (DP) T cells have been described in several species including humans, but their function and immunophenotypic characteristics are still not clearly understood. Here we demonstrate that DP T cells are abundant in the intestinal lamina propria of normal rhesus macaques (Macaca mulatta). Moreover, DP T cells have a memory phenotype and are capable of producing different and/or higher levels of cytokines and chemokines in response to mitogen stimulation compared to CD4 + single-positive T cells. Intestinal DP T cells are also highly activated and have higher expression of CCR5, which makes them preferred targets for simian immunodeficiency virus/HIV infection. Increased levels of CD69, CD25 and HLA-DR, and lower CD62L expression were found on intestinal DP T cells populations compared to CD4 + single-positive T cells. Collectively, these findings demonstrate that intestinal and peripheral blood DP T cells are effector cells and may be important in regulating immune responses, which distinguishes them from the immature DP cells found in the thymus. Finally, these intestinal DP T cells may be important target cells for HIV infection and replication due to their activation, memory phenotype and high expression of CCR5. IntroductionCD4 + CD8 + double positive (DP) T cells in the intestine have been shown to be a major early target in primary simian immunodeficiency virus (SIV) infection [1]. Rapid depletion of intestinal DP cells occurs faster and more profoundly than that of intestinal CD4 + singlepositive (SP) cells which we have previously correlated with increased levels of CCR5 expression on the former [1]. Although DP T cells have been described in the blood and intestine of humans, nonhuman primates, swine and rodents [2][3][4][5][6][7][8][9][10][11][12], little is known regarding their function or immunophenotypic (naive versus memory status etc.) characteristics. DP T cells are perhaps best known in the thymus, where they are T cell precursors in early states of T cell maturation. However, DP T cells in the peripheral blood have been shown to differ from those in the thymus [2].Several investigators have reported the presence of circulating blood DP T cells, in both healthy [13,14] and diseased individuals [15][16][17][18][19][20][21][22]. Existence of this unconventional and rare lymphocyte population in peripheral blood has been hypothesized to result from premature release of immature CD4 + CD8 + T cells from the thymus to the periphery, where their maturation into functionally competent SP cell continues [23]. However, in HIV and Epstein-Barr virus infections, the percentage of DP T cells can increase to 20% of circulating lymphocytes, suggesting they are effector cells responding to infection [14,15]. In humans and animals DP T cells have also been shown to have antiviral activity, further suggesting they are indeed antigen-specific effector cells rather than immature cells from the thymus [2, 4,24]. The intestine is the major target organ of HIV...

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CD4+CD8+ and CD8α+β- T lymphocytes in human small intestinal lamina propria

Cited by 28 publications

References 0 publications

The use of BLT humanized mice to investigate the immune reconstitution of the gastrointestinal tract

The use of BLT humanized mice to investigate the immune reconstitution of the gastrointestinal tract

Neonatal Immunoglobulin Secretion and Lymphocyte Phenotype in Rat Small Intestine Lamina Propria

Intestinal double‐positive CD4⁺CD8⁺ T cells are highly activated memory cells with an increased capacity to produce cytokines

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CD4+CD8+ and CD8α+β- T lymphocytes in human small intestinal lamina propria

Cited by 28 publications

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The use of BLT humanized mice to investigate the immune reconstitution of the gastrointestinal tract

The use of BLT humanized mice to investigate the immune reconstitution of the gastrointestinal tract

Neonatal Immunoglobulin Secretion and Lymphocyte Phenotype in Rat Small Intestine Lamina Propria

Intestinal double‐positive CD4+CD8+ T cells are highly activated memory cells with an increased capacity to produce cytokines

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Intestinal double‐positive CD4⁺CD8⁺ T cells are highly activated memory cells with an increased capacity to produce cytokines