P J L Lane

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..In this review, we concentrate on the latter function: the sustenance by LTis of CD4 T-cell responses for protective immunity...

..Published work links adult lymphoid tissue-inducer cells (LTi) with T cell-dependent antibody responses. In this issue of Immunity, Tsuji et al. (2008) associate LTi with T cell-independent IgA antibody responses in the gut...

..We speculate that their human equivalents could be potential targets for HIV infection and their destruction explains the pattern of loss of CD4 T cells...

..In particular, there have been some key insights into how dendritic cells subsequently direct the evolution of immune responses by differential expression of co-stimulatory molecules...

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..Recent work has revealed the specialization between different dendritic cell subsets and how this relates to their different functions in optimizing T-cell help for antibody responses and inflammatory T-cell responses...

..This would serve to limit inappropriate T cell responses. In contrast, OX40 signals from CD4(+)CD3(-) cells located in the outer T zone select proliferating Th2 effectors into the memory T cell pool...

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..Collectively, our results reveal further complexity in the mechanisms regulating thymus medulla development and highlight the role of distinct TNFRs in initial and terminal differentiation stages in mTECs...

..Our findings show that adult LTi-like cells require extrinsic signals from podoplanin(+) splenic stromal cells to survive and suggest that IL-7 is not necessary to mediate their survival in the adult spleen...

..Our data define the necessity of NK cells for protection of secondary lymphoid organs and describe a mechanism by which this protection is conferred...

..Finally, we show that OX40/CD30 double-knockout OTII transgenic T cells fail to survive compared with normal T cells when cocultured with CD4(+)CD3(-) cells in vitro...

..We propose that the function of CD4+CD3- cells is to form a link between primed CD4 T cells and the underlying stromal elements, creating distinct microenvironments in which they enable effector responses...

..6% for adult CD4(+) and 87.6% for adult CD4(-); 95.3% for embryonic CD4(+) and 91.5% for embryonic CD4(-). Consistently fewer CCR7 single-positive cells were found in the CD4(+) and CD4(-) fractions in the embryo...

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..The model described here demonstrates a method of transferring whole splenic microenvironments and dissecting the stromal and hematopoietic signals involved in spleen development and organization...

..Furthermore, glucocorticoids, which potently suppress T effector function, did not influence the expression of OX40L and CD30L in the presence of IL-7...

..Collectively, our data reveal cellular and molecular mechanisms leading to the generation of Aire(+) mTECs and highlight a previously unrecognized role for CD4(+)3(-)RANKL(+) inducer cells in intrathymic self-tolerance...

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..These results may explain why attenuated Salmonella-induced B cell responses are protective in secondary, but not primary infections...

..Collectively, these data demonstrate that signals through CD30 and OX40 are required for the survival of CD4(+) T cells within the small intestine lamina propria...

..In this review, we concentrate on the role of this cell type in the making of a tolerant CD4 T cell repertoire and in the sustenance of CD4 T cell responses for protective immunity...

..Our studies indicate that a combination of LT signals from LTi cells and LT-independent signals from lymphocytes is sufficient for expression of podoplanin and CCL21 on splenic T cell zone stroma and subsequent T cell organisation...

..Collectively, our data argue against a temporal window of thymocyte crosstalk, and instead demonstrates continued receptiveness of thymic epithelium for the formation of functionally competent thymic microenvironments...

..We summarize current knowledge on the formation of thymic epithelial-cell microenvironments, and highlight similarities between the environments that produce T cells and those that select and maintain them during immune responses...

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..Finally, we demonstrate that this differentiation occurs in vivo: neonatal CD4+ CD3- cells up-regulate both CD30L and OX40L after adoptive transfer into an adult recipient...

..Our data explain how NK cells protect the lymphoid-rich white pulp areas from CMV, allowing protective adaptive T cell-dependent immune responses to develop, and how this mechanism might break down in immunocompromised patients...

..By examining germinal center responses in mice where the ability to signal through T cell CTLA-4 was compromised, we provide data that supports a critical role for CTLA-4 in down-regulating T cell help for germinal center B cells...

..Furthermore, we show that the preferential survival of OX40(+) T cells and support of memory T cell help for B cells are linked to their association with CD4(+)CD3(-) cells in vivo...