We assessed the unprimed bulk and antigen specific CD8+ T cell repertoire in the reconstituted mice for the presence or absence of VM phenotype cells derived from the WT and CD122?/? backgrounds. inexperienced memory space cells which retain the capacity to respond to nominal antigen with memory-like function. Preferential engagement of these Virtual Memory space T cells AZ505 ditrifluoroacetate into a vaccine response could dramatically enhance the rate by which immune protection develops. Intro Memory space phenotype cells arise in a host either as a result of antigenic activation or as a result of homeostatic proliferation (HP) (1). Depending on its context, antigen activation induces the formation of one of a number of memory space cell subsets, each with unique properties with respect to proliferation, trafficking, and effector response (1C3). Similarly, conditions of intense lymphopenia induce the formation of memory space phenotype cells through HP induced by cytokines such as IL-7, IL-12 and IL-15 (4). This form of AZ505 ditrifluoroacetate proliferation results in the manifestation of many, though not all, memory space activation markers and the acquisition of an increased degree of immune protective function relative to na?ve phenotype cells (5C11). While HP requires TCR/MHC relationships (5, 12C14), it does not require or induce overt TCR mediated activation, as evidenced from the differential manifestation of activation markers such as Rabbit polyclonal to HSD3B7 CD49d (15). Until recently, the physiological relevance of HP outside of bone marrow transplantation was unclear, as was the representation of HP memory space T cells within a normal, un-manipulated host. In addition to antigen-mediated and HP memory space cells, the loss of a variety of transcription factors results in the production of so called innate memory space T cells within the thymus, mainly in mice within the BALB/c background, but also to some degree in C57BL/6 animals (B6) (16). These cells are typically CD8+, bear a memory space phenotype, and, like NKT cells, respond to activation by rapid production of IFN when in the periphery. It was recently determined the development of these cells within the thymus requires IL-4 production by PLZF+ iNKT cells (17). The production of innate memory space T cells is definitely amplified in mice deficient in (17C23), (24, 25), (24, 26C29) or (17, 30). A lack of these transcription factors allows an increase in innate memory space cell expansion within the thymus as a result of increased local production of IL-4 (16). It is currently unclear what repertoire of antigen specificities these innate memory space cells might consist of or what the precise practical impact of these cells, in the thymus or periphery, might be in regards to the development of protecting immunity. We and our collaborators recently described a novel subset of memory space phenotype CD8+ T cells that exist in the periphery of normal, lymphoreplete hosts (15). These cells are phenotypically much like both innate memory space cells and HP memory space cells. AZ505 ditrifluoroacetate Further investigation of these memory space phenotype cells exposed that they included cells specific for nominal antigen actually in the absence of earlier antigen exposure. Indeed, their phenotype (CD49dlo) was consistent with their having undergone HP, not with their having responded to antigenic activation. These Virtual Memory space (VM) cells (memory space phenotype cells specific for nominal antigen within an antigen-inexperienced sponsor) bore all the phenotypic and practical hallmarks of HP memory space cells (4) with AZ505 ditrifluoroacetate the notable exception that they were not derived from a lymphopenic environment. These initial observations raised the query whether VM cells were induced from the same thymic processes that produced innate memory space cells or rather by some form of HP.
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