Human Vδ3+ γδ T cells induce maturation and IgM secretion by B cells

Petrasca, Andreea; Melo, Ashanty M; Breen, Edmond J.; Doherty, Derek G.

doi:10.1016/j.imlet.2018.02.002

Cited by 33 publications

(30 citation statements)

References 59 publications

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“…Based on their effector properties, Vγ9Vδ2 + T lymphocytes are believed to play an important role in cellular immune responses against tumors (16) and infectious diseases (17,18). Vδ3 are less well-studied, but also appear to be enriched at mucosal barriers and in the liver (19).…”

Section: Introductionmentioning

confidence: 99%

Unbiased Profiling Reveals Compartmentalization of Unconventional T-Cells Within the Intestinal Mucosa Irrespective of HIV Infection

et al. 2020

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The intestinal mucosa is enriched for unconventional T-cells, including mucosal associated invariant T-cells (MAIT), invariant natural killer T-cells (iNKT) and γδ T-cells. These cells are activated by bacterial metabolites, lipid antigens and cytokines, and are important for intestinal barrier integrity. The loss of gut homeostasis observed in HIV infection is central to disease pathogenesis, and studies have highlighted impairment of particular unconventional T-cell subsets within a specific gut compartment. However, although the small and large intestine are distinct niches, the overall impact of HIV on unconventional T-cells across the gut mucosal has not been well-studied. We hypothesized that compartment specific differences in the unconventional T-cell repertoire would exist between the small and large intestine, due to increasing bacterial loads and microbial diversity; and that the impact of HIV infection might differ depending on the compartment examined. We used mass cytometry, flow cytometry and unbiased T-cell receptor profiling to quantify unconventional T-cells in blood and tissue from the small (duodenum) and large (colon) intestine in HIV infected and uninfected participants undergoing examination for a range of intestinal conditions. Overall, we find distinct compartmentalisation of T-cells between blood, duodenum and colon, with iNKT cells significantly enriched in the duodenum and δ-1 expressing γδ T-cells in the colon. In addition, we observe greater clonal expansion of conventional TCRs in the duodenum, suggestive of stronger adaptive immunity in this compartment. Conversely, we find evidence of an expanded unconventional TCR repertoire in the colon, which contained far more overlapping "donor unrestricted" sequences than the duodenum. Twelve of these TCRs were highly "MAIT-like" and 3 were unique to the colon, suggesting an enrichment of donor unrestricted T-cells (DURTs) in this compartment. Unexpectedly, however, no Magnoumba et al. Unconventional T-Cells and HIV Infection significant impact of HIV infection on any of the unconventional T-cell subsets measured was observed in either mucosal site in terms of frequency or TCR repertoire. Further studies are required to investigate the importance of these unconventional T-cell subsets to intestinal homeostasis within the different gut compartments and determine if they are functionally impaired during HIV infection.

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Section: Introductionmentioning

confidence: 99%

Unbiased Profiling Reveals Compartmentalization of Unconventional T-Cells Within the Intestinal Mucosa Irrespective of HIV Infection

et al. 2020

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“…Vδ3 γδ T cells recognize human leukocyte antigen (HLA)-A2 [30] and CD1d [26], although the specific antigen molecules involved remain unknown. Upon activation, Vδ3 γδ T cells produce IFN-γ, IL-4, and IL-17, thereby promoting Th1, Th2, and Th17 cell differentiation, respectively [31]. Expansion of Vδ1 − Vδ2 − or Vδ3 γδ T cells in the peripheral blood has seldom been reported; indeed, it was only observed upon cytomegalovirus reactivation after renal and stem cell transplantation [32, 33].…”

Section: Discussionmentioning

confidence: 99%

“…The positive correlation between class-switched memory B cells and EDSS scores was not observed in super-responders to IFN-β (NEDA group), possibly because of plateau effects. Vδ3 γδ T cells induce the maturation and IgM secretion of B cells but do not induce class switching to IgG, IgA, or IgE [31]. Rather, Vδ3 γδ T cells exerted cytotoxic functions against CD1d-bearing target cells upon the recognition of CD1d molecules [26, 33].…”

Section: Discussionmentioning

confidence: 99%

Long-term use of interferon-β in multiple sclerosis increases Vδ1−Vδ2−Vγ9− γδ T cells that are associated with a better outcome

Maimaitijiang

Watanabe

Sumii

et al. 2019

J Neuroinflammation

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Background We previously reported that Vδ2+Vγ9+ γδ T cells were significantly decreased in multiple sclerosis (MS) patients without disease-modifying therapies (untreated MS) and were negatively correlated with Expanded Disability Status Scale (EDSS) scores, suggesting protective roles of Vδ2+Vγ9+ γδ T cells. Interferon-β (IFN-β) is one of the first-line disease-modifying drugs for MS. However, no previous studies have reported changes in γδ T cell subsets under IFN-β treatment. Therefore, we aimed to clarify the effects of the long-term usage of IFN-β on γδ T cell subsets in MS patients. Methods Comprehensive flow cytometric immunophenotyping was performed in 35 untreated MS and 21 MS patients on IFN-β for more than 2 years (IFN-β-treated MS) including eight super-responders fulfilling no evidence of disease activity criteria, and 44 healthy controls (HCs). Results The percentages of Vδ2+Vγ9+ cells in γδ T cells were significantly lower in untreated and IFN-β-treated MS patients than in HCs. By contrast, the percentages of Vδ1−Vδ2−Vγ9− cells in γδ T cells were markedly higher in IFN-β-treated MS patients than in HCs and untreated MS patients (both p < 0.001). A significant negative correlation between the percentages of Vδ2+Vγ9+ cells in γδ T cells and EDSS scores was confirmed in untreated MS but not evident in IFN-β-treated MS. Moreover, class-switched memory B cells were decreased in IFN-β-treated MS compared with HCs (p < 0.001) and untreated MS patients (p = 0.006). Interestingly, the percentages of Vδ1−Vδ2−Vγ9− cells in γδ T cells were negatively correlated with class-switched memory B cell percentages in all MS patients (r = − 0.369, p = 0.005), and the percentages of Vδ1−Vδ2−Vγ9− cells in Vδ1−Vδ2− γδ T cells were negatively correlated with EDSS scores only in IFN-β super-responders (r = − 0.976, p < 0.001). Conclusions The present study suggests that long-term usage of IFN-β increases Vδ1−Vδ2−Vγ9− γδ T cells, which are associated with a better outcome, especially in IFN-β super-responders. Thus, increased Vδ1−Vδ2−Vγ9− cells together with decreased class-switched memory B cells may contribute to the suppression of disease activity in MS patients under IFN-β treatment.

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“…More recently, it has been shown that Vδ3 + T-cells can also upregulate CD40, CD86, and HLA-DR and promote the production and the release of IgM, but not IgG, IgA, or IgE by B-cells [42]. Together, these studies suggest that certain γδ T-cells, upon determinate conditions, can acquire a role similar to the Tfh [24].…”

Section: How Do γδ T-cells Influence B-cells?mentioning

confidence: 99%

Revisiting the Interaction of γδ T-Cells and B-Cells

Rampoldi

Ullrich

Prinz

2020

Cells

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Right after the discovery of γδ T-cells in 1984, people started asking how γδ T-cells interact with other immune cells such as B-cells. Early reports showed that γδ T-cells are able to help B-cells to produce antibodies and to sustain the production of germinal centers. Interestingly, the presence of γδ T-cells seems to promote the generation of antibodies against "self" and less against challenging pathogens. More recently, these hypotheses were supported using γδ T-cell-deficient mouse strains, in different mouse models of systemic lupus erythematous, and after induction of epithelial cell damage. Together, these studies suggest that the link between γδ T-cells and the production of autoantibodies may be more relevant for the development of autoimmune diseases than generally acknowledged and thus targeting γδ T-cells could represent a new therapeutic strategy. In this review, we focus on what is known about the communication between γδ T-cells and B-cells, and we discuss the importance of this interaction in the context of autoimmunity.

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Human Vδ3+ γδ T cells induce maturation and IgM secretion by B cells

Cited by 33 publications

References 59 publications

Unbiased Profiling Reveals Compartmentalization of Unconventional T-Cells Within the Intestinal Mucosa Irrespective of HIV Infection

Unbiased Profiling Reveals Compartmentalization of Unconventional T-Cells Within the Intestinal Mucosa Irrespective of HIV Infection

Long-term use of interferon-β in multiple sclerosis increases Vδ1−Vδ2−Vγ9− γδ T cells that are associated with a better outcome

Revisiting the Interaction of γδ T-Cells and B-Cells

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