Similar Datasets
Project description:Gamma Delta (gd) T cells play unique protective roles in different settings of acute and chronic infections. However, what they respond to and how they function in the acute versus chronic phases of the same infection remains unclear. It is well documented that cytolytic gd T cells that express Vg9Vd2 TCRs and respond to phosphoantigens (pAgs) expand in acute Mycobacterium tuberculosis (Mtb) infection in humans. However, most infections with Mtb manifest as a chronic, clinically asymptomatic state. While past work indicates that gd T cells contribute to Mtb infection control, their response during this phase of Mtb infection is not well understood. Here, we analyze peripheral blood gd T cells from a South African adolescent cohort and show that a unique CD8+ gd T cell subset with features of “memory inflation” expand in chronic Mtb infection. Using targeted scRNA-seq coupled with surface protein expression and multiparametric single cell pseudotime trajectory analysis, we identify the differentiation paths that these CD8+ gd T cells follow to develop into effectors in this infection state.
2022-10-31 | GSE216654 | GEO
Project description:Gamma Delta (gd) T cells play unique protective roles in different settings of acute and chronic infections. However, what they respond to and how they function in the acute versus chronic phases of the same infection remains unclear. It is well documented that cytolytic gd T cells that express Vg9Vd2 TCRs and respond to phosphoantigens (pAgs) expand in acute Mycobacterium tuberculosis (Mtb) infection in humans. However, most infections with Mtb manifest as a chronic, clinically asymptomatic state. While past work indicates that gd T cells contribute to Mtb infection control, their response during this phase of Mtb infection is not well understood. Here, we analyze peripheral blood gd T cells from a South African adolescent cohort and show that a unique CD8+ gd T cell subset with features of “memory inflation” expand in chronic Mtb infection.
2022-10-31 | GSE216652 | GEO
Project description:Antigen-expanded CD8+ gd T cells with NK-like phenotype and function respond in persistent infection
| PRJNA894700 | ENA
Project description:Antigen-expanded CD8+ gd T cells with NK-like phenotype and function respond in persistent infection [scRNA-seq]
| PRJNA894703 | ENA
Project description:Antigen-expanded CD8+ gd T cells with NK-like phenotype and function respond in persistent infection [Bulk RNA-seq]
| PRJNA894702 | ENA
Project description:The response of gamma delta (γδ) T cells in the acute versus chronic phases of the same infection is unclear. How γδ T cells function in acute Mycobacterium tuberculosis (Mtb) infection is well characterized, but their response during persistent Mtb infection is not well understood, even though most infections with Mtb manifest as a chronic, clinically asymptomatic state. Here, we analyze peripheral blood γδ T cells from a South African adolescent cohort and show that a unique CD8+ γδ T cell subset with features of "memory inflation" expands in chronic Mtb infection. These cells are hyporesponsive to T cell receptor (TCR)-mediated signaling but, like NK cells, can mount robust CD16-mediated cytotoxic responses. These CD8+ γδ T cells comprise a highly focused TCR repertoire, with clonotypes that are Mycobacterium specific but not phosphoantigen reactive. Using multiparametric single-cell pseudo-time trajectory analysis, we identified the differentiation paths that these CD8+ γδ T cells follow to develop into effectors in this infection state. Last, we found that circulating CD8+ γδ T cells also expand in other chronic inflammatory conditions, including cardiovascular disease and cancer, suggesting that persistent antigenic exposure may drive similar γδ T cell effector programs and differentiation fates.
| S-EPMC10408713 | biostudies-literature
Project description:Osteoclasts (OCs) and much less dendritic cells (DCs) induce significant expansion and functional activation of NK cells, and furthermore, the OC-expanded NK cells preferentially increase the expansion and activation of CD8+ T cells by targeting CD4+ T cells. When autologous OCs were used to expand patient NK cells much lower percentages of expanded CD8+ T cells, decreased numbers of expanded NK cells and decreased functions of NK cells could be observed, and the addition of allogeneic healthy OCs increased the patients' NK function. Mechanistically, OC-expanded NK cells were found to lyse CD4+ T cells but not CD8+ T cells suggesting potential selection of CD8+ T cells before their expansion by OC activated NK cells. In agreement, Increased IFN-γ secretion, and NK cell-mediated cytotoxicity and higher percentages of CD8+ T cells, in various tissue compartments of oral tumor-bearing hu-BLT mice in response to immunotherapy by OC-expanded NK cells were observed. Thus, our results indicate an important relationship between NK and CD8+ T cells.
| S-EPMC7683603 | biostudies-literature
Project description:IntroductionPolymorphisms in the type III interferon IFN-λ3 and the killer cell immunoglobulin-like receptor (KIR) genes controlling the activity of natural killer (NK) cells can predict spontaneous resolution of acute hepatitis C virus (HCV) infection. We hypothesized that IFN-λ3 polymorphism may modulate NK cell function during acute HCV.MethodsWe monitored the plasma levels of type III IFNs in relation to the phenotype and the function of NK cells in a cohort of people who inject drugs (PWID) during acute HCV infection with different outcomes.ResultsEarly acute HCV was associated with high variability in type III IFNs plasma levels and the favorable IFN-λ3 CC genotype was associated with higher viral loads. Reduced expression of Natural Killer Group Protein 2A (NKG2A) was associated with lower IFN-λ3 plasma levels and the CC genotype. IFN-γ production by NK cells was higher in individuals with the CC genotype during acute infection but this did not prevent viral persistence. IFN-λ3 plasma levels did not correlate with function of NK cells and IFN-λ3 prestimulation did not affect NK cell activation and function.ConclusionsThese results suggest that IFN-λ3 polymorphism indirectly influences NK cell phenotype and function during acute HCV but other factors may act in concert to determine the outcome of the infection.
| S-EPMC5004291 | biostudies-literature
Project description:Cytomegalovirus (CMV) reactivation remains a common complication and leads to high mortality in patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT). Early natural killer (NK) cell reconstitution may protect against the development of human CMV (HCMV) infection post-HSCT. Our previous data showed that ex vivo mbIL21/4-1BBL-expanded NK cells exhibited high cytotoxicity against leukemia cells. Nevertheless, whether expanded NK cells have stronger anti-HCMV function is unknown. Herein, we compared the anti-HCMV functions of ex vivo expanded NK cells and primary NK cells. Expanded NK cells showed higher expression of activating receptors, chemokine receptors and adhesion molecules; stronger cytotoxicity against HCMV-infected fibroblasts; and better inhibition of HCMV propagation in vitro than primary NK cells. In HCMV-infected humanized mice, expanded NK cell infusion resulted in higher NK cell persistence and more effective tissue HCMV elimination than primary NK cell infusion. A clinical cohort of 20 post-HSCT patients who underwent adoptive NK cell infusion had a significantly lower cumulative incidence of HCMV infection (HR = 0.54, 95% CI = 0.32-0.93, p = 0.042) and refractory HCMV infection (HR = 0.34, 95% CI = 0.18-0.65, p = 0.009) than controls and better NK cell reconstitution on day 30 post NK cell infusion. In conclusion, expanded NK cells exhibit stronger effects than primary NK cells against HCMV infection both in vivo and in vitro.
| S-EPMC10387476 | biostudies-literature
Project description:Inhibition of type 1 interferon (IFN-I) signaling promotes the control of persistent virus infection, but the underlying mechanisms remain poorly understood. Here, we report that genetic ablation of Ifnar1 specifically in natural killer (NK) cells led to elevated numbers of T follicular helper cells, germinal center B cells, and plasma cells and improved antiviral T cell function, resulting in hastened virus clearance that was comparable to IFNAR1 neutralizing antibody treatment. Antigen-specific B cells and antiviral antibodies were essential for the accelerated control of LCMV Cl13 infection following IFNAR1 blockade. IFNAR1 signaling in NK cells promoted NK cell function and general killing of antigen-specific CD4 and CD8 T cells. Therefore, inhibition of IFN-I signaling in NK cells enhances CD4 and CD8 T cell responses, promotes humoral immune responses, and thereby facilitates the control of persistent virus infection.
| S-EPMC7997497 | biostudies-literature