Project description:gd T cell infiltration into tumours usually correlates with improved patient outcome, but both tumour-promoting and tumoricidal effects of γδ T cells have been documented. Human γδ T cells can be divided into functionally distinct subsets based on T cell receptor Vd usage. Still, the contribution of these different subsets to tumour immunity remains elusive. Here, we provide a detailed gd T cell profiling in colon tumours, comprising mRNA quantification using the Nanostring platform, in combination with mass and flow cytometry and TCR sequencing. δ chain usage in both the macroscopically unaffected colon mucosa and tumours varied considerably between patients, with substantial fractions of Vδ1, Vδ2, and non-Vd1Vd2 cells. Nanostring analyses of flow cytometry sorted Vd1, Vd2 and non-Vd1Vd2 cells showed a large variation in gd T cell subsets between individual tumours, and we suggest that individual gd T cell composition in colon tumours may contribute to the balance between favourable and adverse immune responses, and thereby also patient outcome.
Project description:Mechanistic Insights. Our study reveals the crucial role of gammadelta T cells in non-tuberculous mycobacteria (NTM) infection. We observed a significant increase and activation of gammadelta T cells in mice infected with MAB or with MAB infection combined with pulmonary fibrosis. Depletion of gammadelta T cells worsened the infection, while transfer of gammadelta T cells reversed this effect. Mechanistically, we found that MAB infection stimulates macrophages to produce IL-1beta and IL-23, which promotes the expansion of gammadelta T17 cells. MAB can also directly activate gammadelta T cells, leading to the clearance of MAB through an IL-17A-dependent pathway. Our findings suggest that gammadelta T cells represent a potential therapeutic target for NTM infections.
Project description:Mechanistic Insights. Our study reveals the crucial role of gammadelta T cells in non-tuberculous mycobacteria (NTM) infection. We observed a significant increase and activation of gammadelta T cells in mice infected with MAB or with MAB infection combined with pulmonary fibrosis. Depletion of gammadelta T cells worsened the infection, while transfer of gammadelta T cells reversed this effect. Mechanistically, we found that MAB infection stimulates macrophages to produce IL-1beta and IL-23, which promotes the expansion of gammadelta T17 cells. MAB can also directly activate gammadelta T cells, leading to the clearance of MAB through an IL-17A-dependent pathway. Our findings suggest that gammadelta T cells represent a potential therapeutic target for NTM infections.
Project description:Mechanistic Insights. Our study reveals the crucial role of gammadelta T cells in non-tuberculous mycobacteria (NTM) infection. We observed a significant increase and activation of gammadelta T cells in mice infected with MAB or with MAB infection combined with pulmonary fibrosis. Depletion of gammadelta T cells worsened the infection, while transfer of gammadelta T cells reversed this effect. Mechanistically, we found that MAB infection stimulates macrophages to produce IL-1beta and IL-23, which promotes the expansion of gammadelta T17 cells. MAB can also directly activate gammadelta T cells, leading to the clearance of MAB through an IL-17A-dependent pathway. Our findings suggest that gammadelta T cells represent a potential therapeutic target for NTM infections.
Project description:We compared gammadelta T-cell development and subsets in the thymus of mice in which Shh had been conditionally deleted from thymic epithelial cells using FoxN1-Cre to WT mice, and to transgenic mice in which a constitutively activator (Gli2DN2) or constitutuvely repressor (Gli2DC2) form of Gli2 were expressed under the control of the lck-promotor. We sorted CD27+CD3+TCR-gammadelta+ cells from 4 week old mice and comapred gene expression by RNAsequencing. All mice were on a C57BL/6 background.