Diverse populations of T cells with NK cell receptors accumulate in the human intestine in health and in colorectal cancer

O’Keeffe, Joan; Doherty, Derek G.; Kenna, Tony J.; Sheahan, Kieran; O’Donoghue, Diarmuid; Hyland, John; O’Farrelly, Cliona

doi:10.1002/eji.200424958

Cited by 74 publications

(103 citation statements)

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“…1B). Significant variation in CD56 ϩ T cell frequency was detected in the colon and small bowel (ranging 2-36 and 5-33%, respectively), in agreement with a study by Pittet et al (39), although lower frequency variations were reported in a second smaller cohort (16). Further analysis of colonic specimens from inflamed and uninvolved intestinal sites indicated reduced frequencies of CD56 ϩ T cells in inflamed sites ( p Ͻ 0.0001 vs non-IBD and p Ͻ 0.0028 vs uninvolved), whereas frequencies in uninvolved sites did not significantly differ from non-IBD mucosa (Fig.…”

Section: Cd56supporting

confidence: 91%

“…CD56 T cells were detected by surface immunostaining and flow cytometric analysis of lymphocytes isolated from the human intestinal LP (LP lymphocytes), MLNs, or peripheral blood (PB). Scatter plot analysis of gated live lymphocytes re- (16). CD56 staining intensity in CD3 ϩ T cell population was relatively low and almost exclusively corresponded to the CD56 dim profile, characteristic of a functionally distinct subset of NK cells (31), whereas CD3…”

Section: Cd56mentioning

confidence: 92%

“…Cong et al (14) further established a requirement for effector T cell "priming" by intestinal commensal bacteria, and recent studies reported key roles for B and NKT cells in the maintenance of intestinal immune homeostasis (15) and immune suppression (13). In humans, several functionally distinct T cell populations have been reported in the gut mucosa, such as T cells expressing NK markers (16). For instance, intestinal T cells expressing CD161 were recently reported to express proinflammatory cytokines (17), whereas a second population of mucosal T cells expresses CD56 (18), a marker which may identify proinflammatory T cells in the liver (19,20).…”

Section: Cd56 Marks An Effector T Cell Subset In the Humanmentioning

confidence: 99%

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CD56 Marks an Effector T Cell Subset in the Human Intestine

Cohavy

Targan

2007

The Journal of Immunology

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T cells are key mediators of intestinal immunity, and specific T cell subsets can have differing immunoregulatory roles in animal models of mucosal inflammation. In this study, we describe human CD56+ T cells as a morphologically distinct population expressing a mature, nonproliferative phenotype that is frequent in the gut. Enhanced potential for IFN-γ and TNF synthesis suggested a proinflammatory function, and we directly demonstrate effector function mediated by direct T-T interaction with responder cells in vitro. CD56+ T cells from peripheral blood responded to the gut-related CD2 signal, and were necessary for effective CD2-mediated proliferation of peripheral blood CD56− T cells. Our findings associate CD56+ T cells with the intestinal immune compartment and suggest a putative effector function in human mucosal immunity.

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Section: Cd56supporting

confidence: 91%

Section: Cd56mentioning

confidence: 92%

Section: Cd56 Marks An Effector T Cell Subset In the Humanmentioning

confidence: 99%

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CD56 Marks an Effector T Cell Subset in the Human Intestine

Cohavy

Targan

2007

The Journal of Immunology

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“…Only a small minority of human CD161 ϩ T cells are NK T cells with the invariant TCR (V␣24V␤11), because the latter cells represent no less than 1% of all T cells in the lymphoid tissues and liver (12,13). Although, CD161 is expressed on the minority of human blood T cells, CD161 ϩ T cells expressing either CD4 or CD8 represented the majority of T cells from the epithelial and lamina propria layers of the human duodenum and colon (14). The latter cells contained few, if any, V␣24V␤11 invariant NK T cells and secreted IFN-␥ and TNF-␣ without IL-4 after in vitro stimulation.…”

Section: Expression Of Cd161 (Nkr-mentioning

confidence: 99%

Expression of CD161 (NKR-P1A) Defines Subsets of Human CD4 and CD8 T Cells with Different Functional Activities

Takahashi

Dejbakhsh-Jones

Strober

2006

The Journal of Immunology

128

116

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A subset of T cells in human peripheral blood expresses CD161 (NKR-P1A) receptors that are primarily associated with NK cells. In the current study we isolated blood T cell subsets according to the expression of CD161 and examined their contents of naive, central memory, and effector memory cells and their capacities for proliferation, cytokine secretion, and natural cytolysis. We found that CD4+CD161− and CD8+CD161− subsets contained predominantly naive T cells that secreted high levels of IL-2 after in vitro stimulation, and CD4+CD161int and CD8+CD161int subsets contained predominantly effector and central memory T cells that secreted high levels of IFN-γ and TNF-α. All of these subsets showed vigorous proliferation after stimulation in vitro, but none had NK lytic activity. Unexpectedly, the CD8+CD161+ cells contained an anergic CD8α+CD8βlow/−CD161high T cell subset that failed to proliferate, secrete cytokines, or mediate NK lytic activity.

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“…[10][11][12] The frequency of these cells varies in certain pathologic conditions, such as cancer and viral or autoimmune diseases. [12][13][14][15] Recently, it has been demonstrated that a subset of naive cord blood CD4 T cells express CD161 and are precursors of peripheral, mature, Th17 T cells. 16 CD161 expression seems to correlate with interleukin-17 (IL-17) secretion by CD4 T cells.…”

Section: Introductionmentioning

confidence: 99%

Human MAIT cells are xenobiotic-resistant, tissue-targeted, CD161hi IL-17–secreting T cells

Dusséaux

Martin

Serriari

et al. 2011

Blood

873

1,376

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Mucosal-associated invariant T (MAIT) cells IntroductionMainstream T cells display a very diverse repertoire of antigen receptors, which enable these cells to respond to a wide variety of antigens presented by polymorphic major histocompatibility complex (MHC) molecules. During development, interactions between the T cells and selecting MHC class II and I molecules on thymic epithelial cells lead to the specific features of CD4 and CD8 T-cell lineage. However, 2 "innate-like" T lymphocytes, the natural killer T (NKT) and mucosal-associated invariant T (MAIT) cells, follow different ontogenic pathways with selection by nonpolymorphic MHC class Ib molecules. 1 Human MAIT cells express the semi-invariant T-cell receptor (TCR; iV␣7.2-J␣33) and are selected by the MHC class Ib molecule, MR1 on hematopoietic cells, which confer peculiar features. 2,3 Indeed, MAIT cells are enriched in the intestinal lamina propria and are numerous in the peripheral blood of healthy subjects. They are present in cord blood in small numbers with a naive phenotype, whereas in adults they represent approximately 10% of mature CD8 or CD4 Ϫ CD8 Ϫ (DN) T cells and display an effector-memory phenotype. We recently showed that MAIT cells specifically react against antigen-presenting cells (APCs), fed with a wide variety of bacteria and yeasts but not viruses, and display protective activity in experimental bacterial infection models. 4,5 In humans, they are defined as CD161 hi IL-18R␣ ϩ V␣7.2 ϩ ␥␦ Ϫ CD3 ϩ lymphocytes. 3,4 Either CD161 or IL-18R␣ expression at the cell surface, together with the V␣7.2 segment, allows for the unequivocal identification of MAIT cells in both peripheral blood and tissues. 3,4 CD161 (KLRB1, NKRP1A) is a C-type lectin family member, part of the NK complex. 6 Ligands for CD161 have been described only recently, and blocking or cross-linking CD161 may modulate T-cell functions. 7-9 CD161 is also expressed by the majority of NK cells and diverse subsets of T lymphocytes that include TCR-␥␦ T cells and most NKT cells. CD161 expression is found on a significant proportion of tissue-infiltrating T cells, such as the intestine and liver. [10][11][12] The frequency of these cells varies in certain pathologic conditions, such as cancer and viral or autoimmune diseases. [12][13][14][15] Recently, it has been demonstrated that a subset of naive cord blood CD4 T cells express CD161 and are precursors of peripheral, mature, Th17 T cells. 16 CD161 expression seems to correlate with interleukin-17 (IL-17) secretion by CD4 T cells. 17 Among TCR-␣␤ T cells, most of the CD161 ϩ T cells belong to the CD4 subset. However, CD8 T cells expressing CD161 can also be found, but their nature has just begun to be explored. CD161 ϩ CD8 T cells can be split into 2 different populations expressing intermediate or high levels of CD161. Two recent reports independently raised new findings on this latter subset. The first shows that CD161 hi CD8 T cells represent self-renewing memory cells, which survive chemotherapy. 18 These cells are absent from...

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Diverse populations of T cells with NK cell receptors accumulate in the human intestine in health and in colorectal cancer

Cited by 74 publications

References 50 publications

CD56 Marks an Effector T Cell Subset in the Human Intestine

CD56 Marks an Effector T Cell Subset in the Human Intestine

Expression of CD161 (NKR-P1A) Defines Subsets of Human CD4 and CD8 T Cells with Different Functional Activities

Human MAIT cells are xenobiotic-resistant, tissue-targeted, CD161hi IL-17–secreting T cells

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