Phenotypic and functional heterogeneity are the hallmarks of effector and memory T cells. Upon antigen stimulation, y T cells differentiate into two major types of memory T cells： central memory cells, which patrol t...Phenotypic and functional heterogeneity are the hallmarks of effector and memory T cells. Upon antigen stimulation, y T cells differentiate into two major types of memory T cells： central memory cells, which patrol the blood and secondary lymphoid organs, and effector memory cells, which migrate to peripheral tissues, y T cells display in vitroa certain degree of plasticity in their function that is reminiscent of that which is observed in conventional CD4 T cells. Similar to CD4 T cells, in which a plethora of specialized subsets affect the host response, y8 T cells may readily and rapidly assume distinct Thl-, Th2-, Th17-, TFH and T regulatory-like effector functions, suggesting that they profoundly influence cell-mediated and humoral immune responses. In addition to differences in cytokine repertoire, y~ T cells exhibit diversity in homing, such as migration to lymph node follicles, to help B cells versus migration to inflamed tissues. Here, we review our current understanding of y T-cell lineage heterogeneity and flexibility, with an emphasis on the human system, and propose a classification of effector y T cells based on distinct functional phenotypes.展开更多
Vy2Vδ2 T （also known as Vy9Vδ2 T） cells exist only in primates, and in humans represent a major yδ T-cell sub-population in the total population of circulating yδ T cells. Results from recent studies suggest tha...Vy2Vδ2 T （also known as Vy9Vδ2 T） cells exist only in primates, and in humans represent a major yδ T-cell sub-population in the total population of circulating yδ T cells. Results from recent studies suggest that while （E）-4-hydroxy-3-methyl-but-2-enyl pyrophosphate （HMBPP） phosphoantigen from Mycobacterium tuberculosis （Mtb） and other microbes activates and expands primate Vy2Vδ2 T cells, the Vy2Vδ2 T-cell receptor （TCR） recognizes and binds to HMBPP on antigen-presenting cells （APC）. In response to HMBPP stimulus, Vy2V82 TCRs array to form signaling-related nanoclusters or nanodomains during the activation of Vy2V82 T cells. Primary infections with H MBPP-producing pathogens drive the evolution of multieffector functional responses in Vy2Vδ2 T cells, although Vy2V82 T cells display different patterns of responses during the acute and chronic phases of Mtb infection and in other infections. Expanded Vy2Vδ2 T cells in primary Mtb infection can exhibit a broader TCR repertoire and a greater clonal response than previously assumed, with different distribution patterns of Vδ,2Vδ2 T-cell clones in lymphoid and non-lymphoid compartments. Emerging in vivo data suggest that HMBPP activation of Vy2W2 T cells appears to impact other immune cells during infection.展开更多
文摘Phenotypic and functional heterogeneity are the hallmarks of effector and memory T cells. Upon antigen stimulation, y T cells differentiate into two major types of memory T cells： central memory cells, which patrol the blood and secondary lymphoid organs, and effector memory cells, which migrate to peripheral tissues, y T cells display in vitroa certain degree of plasticity in their function that is reminiscent of that which is observed in conventional CD4 T cells. Similar to CD4 T cells, in which a plethora of specialized subsets affect the host response, y8 T cells may readily and rapidly assume distinct Thl-, Th2-, Th17-, TFH and T regulatory-like effector functions, suggesting that they profoundly influence cell-mediated and humoral immune responses. In addition to differences in cytokine repertoire, y~ T cells exhibit diversity in homing, such as migration to lymph node follicles, to help B cells versus migration to inflamed tissues. Here, we review our current understanding of y T-cell lineage heterogeneity and flexibility, with an emphasis on the human system, and propose a classification of effector y T cells based on distinct functional phenotypes.
文摘Vy2Vδ2 T （also known as Vy9Vδ2 T） cells exist only in primates, and in humans represent a major yδ T-cell sub-population in the total population of circulating yδ T cells. Results from recent studies suggest that while （E）-4-hydroxy-3-methyl-but-2-enyl pyrophosphate （HMBPP） phosphoantigen from Mycobacterium tuberculosis （Mtb） and other microbes activates and expands primate Vy2Vδ2 T cells, the Vy2Vδ2 T-cell receptor （TCR） recognizes and binds to HMBPP on antigen-presenting cells （APC）. In response to HMBPP stimulus, Vy2V82 TCRs array to form signaling-related nanoclusters or nanodomains during the activation of Vy2V82 T cells. Primary infections with H MBPP-producing pathogens drive the evolution of multieffector functional responses in Vy2Vδ2 T cells, although Vy2V82 T cells display different patterns of responses during the acute and chronic phases of Mtb infection and in other infections. Expanded Vy2Vδ2 T cells in primary Mtb infection can exhibit a broader TCR repertoire and a greater clonal response than previously assumed, with different distribution patterns of Vδ,2Vδ2 T-cell clones in lymphoid and non-lymphoid compartments. Emerging in vivo data suggest that HMBPP activation of Vy2W2 T cells appears to impact other immune cells during infection.
