Project description:To characterize the FcRL3+ T cell subset in memory helper CD4+, CD8+, and CD4+ regulatory lymphocytes, we performed RNA-sequencing analysis using T cells, separated by the expression of FcRL3, from the peripheral blood of 5 healthy donors, stimulated for 3h with PMA and ionomycin to induce cytokine expression.
Project description:CD4+ T lymphocytes are key to immunological memory, but little is known about the lifestyle of memory CD4+ T lymphocytes. We showed that in the memory phase of specific immune responses to antigens, most of the memory CD4+ T lymphocytes relocated into the bone marrow (BM) within 3-8 weeks after their generation, a process involving integrin a2. Antigen-specific memory CD4+ T lymphocytes expressed Ly-6C to a high degree, unlike most splenic CD44hiCD62L- CD4+ T lymphocytes. In adult mice, more than 80% of Ly-6Chi CD44hiCD62L- memory CD4+ T lymphocytes were in the BM. In the BM, they are located next to IL-7-expressing VCAM-1+ stroma cells, and were in a resting state. Upon challenge with antigen, they rapidly expressed cytokines and CD154 and induced the production of high-affinity antibodies, indicating their functional activity in vivo and marking them as professional memory T helper cells
Project description:To understand tissue resident features of memory CD4+ and CD8+ T lymphocytes of the bone marrow and/or spleen according to expressing or not the tissue retention marker CD69, we performed whole transcriptome profiling of ex vivo antigen-specific CD69+ and CD69- memory CD4+ T cells isolated from bone marrow and spleen, and ex vivo CD69+ and CD69- memory CD8+ T cells isolated from bone marrow.
Project description:Using scRNA-seq we investigate the impact of the absence of MYC on physio-pathological development of PTEN-proficient or PTEN-deficient T lymphocytes. We demonstrate that MYC-deficient effector/memory T cells is drastically reduced. MYC is then essential for effector/memory differentiation
Project description:Understanding the mechanisms that modulate T helper lymphocyte functions is crucial to decipher normal and pathogenic immune responses in humans. To identify molecular determinants influencing the pathogenicity of T cells, we separated ex vivo-isolated primary human memory T lymphocytes based on their ability to produce high levels of inflammatory cytokines. We found that the inflammatory, cytokine-producing phenotype of memory T lymphocytes was defined by a specific core gene signature and was mechanistically regulated by the constitutive activation of the NF-kB pathway and by the expression of the transcriptional repressor BHLHE40. BHLHE40 attenuated the expression of anti-inflammatory factors, including miR-146a, a negative regulator of NF-kB activation, and ZC3H12D, an RNase of the Regnase-1 family able to degrade inflammatory transcripts. Our data reveal a molecular network regulating the pro-inflammatory phenotype of human memory T lymphocytes, with the potential to contribute to disease.
Project description:Lymphocyte differentiation depends on activation via antigen and cytokines during the immune response to infection. How the timing and integration of these signals program the epigenetic and functional fate of these cells is not completely understood. In this study, we find that inflammatory cytokine signals received by innate and adaptive lymphocytes have a context-dependent role for immune memory formation. Without preceding and sufficient antigen receptor signaling, inflammatory cytokines drive terminal differentiation into short-lived effector cells. In contrast, sufficient antigen-receptor signaling redirects inflammatory cytokine signals to promote memory differentiation via cooperation of STAT and AP-1 transcription factors. By this crucial epigenetic mechanism, optimally equipped lymphocytes are selected for memory formation rather than a terminal effector cell fate. Whereas T cells are hardwired to be shielded from premature inflammatory signals, NK cells rely on coincidental early antigen receptor signaling for adaptive responses. Together, step-wise integration of antigen and cytokine signaling optimizes both effector and memory differentiation, allowing for promiscuous recruitment into the acute immune response while promoting avidity maturation in memory populations of both innate and adaptive lymphocytes.
Project description:Lymphocyte differentiation depends on activation via antigen and cytokines during the immune response to infection. How the timing and integration of these signals program the epigenetic and functional fate of these cells is not completely understood. In this study, we find that inflammatory cytokine signals received by innate and adaptive lymphocytes have a context-dependent role for immune memory formation. Without preceding and sufficient antigen receptor signaling, inflammatory cytokines drive terminal differentiation into short-lived effector cells. In contrast, sufficient antigen-receptor signaling redirects inflammatory cytokine signals to promote memory differentiation via cooperation of STAT and AP-1 transcription factors. By this crucial epigenetic mechanism, optimally equipped lymphocytes are selected for memory formation rather than a terminal effector cell fate. Whereas T cells are hardwired to be shielded from premature inflammatory signals, NK cells rely on coincidental early antigen receptor signaling for adaptive responses. Together, step-wise integration of antigen and cytokine signaling optimizes both effector and memory differentiation, allowing for promiscuous recruitment into the acute immune response while promoting avidity maturation in memory populations of both innate and adaptive lymphocytes.