The paucity of lymph node T cells (plt) mutation leads to a loss of CCL21 and CCL19 expression in secondary lymphoid organs. plt mice have defects in the migration of naive T cells and activated dendritic cells into the T cell zones of lymphoid organs, suggesting that they would have defects in T cell immune responses. We now demonstrate T cell responses in plt mice are delayed but ultimately enhanced. Responses to contact sensitization are decreased at day 2 after priming but increased at day 6. After subcutaneous immunization, antigen-specific T cell proliferation and cytokine production in plt mice are increased and remain markedly elevated for at least 8 wk. Compared with wild-type mice, a proportion of T cell response in plt mice are shifted to the spleen, and prior splenectomy reduces the T cell response in draining lymph nodes. After immunization of plt mice, T cells and dendritic cells colocalize in the superficial cortex of lymph nodes and in splenic bridging channels, but not in T cell zones. These results demonstrate that plt mice mount robust T cell responses despite the failure of naive T cells and activated dendritic cells to enter the thymus dependent areas of secondary lymphoid organs.

CCL19 and CCL21 are thought to be critical for experimental autoimmune encephalomyelitis (EAE) induction, but their precise role is unknown. We examined the role of these chemokines in inducing EAE. C57BL/6 mice lacking expression of these chemokines (plt/plt mice) or their receptor CCR7 were resistant to EAE induced with myelin oligodendrocyte glycoprotein peptide 35–55 (MOG35–55) and pertussis toxin. However, passive transfer of pathogenic T cells from wild-type mice induced EAE in plt/plt mice, suggesting a defect independent of the role of CCR7 ligands in the migration of immune cells. Examination of draining lymph node (DLN) cells from MOG35–55-immunized plt/plt mice found decreased IL-23 and IL-12 production by plt/plt dendritic cells (DCs) and a concomitant defect in Th17 cell and Th1 cell generation. In contrast, production of the Th17 lineage commitment factors IL-6 and TGF-β were unaffected by loss of CCR7 ligands. The adoptive transfer of in vitro-generated Th17 cells from DLN cells of MOG35–55-immunized plt/plt mice developed EAE in wild-type recipient mice, whereas that of Th1 cells did not. Pathogenic Th17 cell generation was restored in plt/plt DLNs with the addition of exogenous IL-23 or CCL19/CCL21 and could be reversed by inclusion of anti-IL-23 mAb in cultures. Exogenous CCL19/CCL21 induced IL-23p19 expression and IL-23 production by plt/plt or wild-type DCs. Therefore, CCR7 ligands have a novel function in stimulating DCs to produce IL-23 and are important in the IL-23-dependent generation of pathogenic Th17 cells in EAE induction.

As the anatomical characteristic of the short external rotators, the root of the internal obturator muscle is connected to the levator ani muscle. Among the pelvic floor muscles, this levator ani muscle is closely involved in supporting the pelvic organs. Since the short external rotators may have been atrophied due to hip joint dysfunction before surgery, if the strength of this muscle group recovers, support of the pelvic organs and urinary incontinence may be improved. It was assumed that surgery through AA improved external rotation contracture of the hip joint and leg length, which increased tension of the internal obturator muscle, with which tension of the pelvic floor muscle also increased and improved urinary incontinence.

IntroductionActivation of naive T cells through engagement of the T-cell receptor (TCR) by antigen leads to proliferation and differentiation into helper and cytotoxic T cells. After expansion of antigenspecific T cells, the majority of the effector cells die to prevent undesirable immune responses such as autoimmunity, 1,2 whereas a portion of them survive as memory T cells. One way homeostasis is maintained is the clearance of effector T cells through activationinduced cell death (AICD), in which activated T cells are triggered through various means to die by apoptosis. [1][2][3][4] The importance of the lymphoid organ microenvironment in regulation of T-cell responses has been suggested by a previous report, in which promotion of T-cell retention in lymphoid organs by a sphingosinederived drug, FTY720, suppresses in vivo T-cell responses. 5 Secondary lymphoid organ T-cell zones contain antigen-presenting cells and stromal cells secreting various cytokines and chemokines with potential to regulate T-cell responses, but the roles of these cells in promoting T-cell AICD are mostly unknown.The chemokines CCL19 and CCL21 are expressed by stromal cells in the T-cell zone of secondary lymphoid tissues. 6,7 Additionally, a subset of dendritic cells (DCs) in the T-cell zone has also been shown to produce CCL19. 8 There are 2 types of CCL21 in mouse; CCL21-Ser, which is expressed on high endothelial venules and in the T-cell zone of secondary lymphoid organs, and CCL21-Leu, which is expressed only in the lymphatic endothelium. 6,7,9,10 CCL19 and CCL21 attract cells expressing their common receptor CCR7. 11,12 These 2 chemokines mobilize naive or central memory T (T CM ) cells and mature DCs to the T-cell zone, [13][14][15][16] and thus can potentially affect T-cell responses.We previously reported that plt/plt mice lacking CCL19 and CCL21 expression in secondary lymphoid tissues due to the lack of CCL19 and CCL21-Ser genes exhibit delayed but ultimately enhanced T-cell responses. 10,17,18 Further, the T-cell responses in plt/plt mice persist for a long time, a phenomenon never observed in wild-type (WT) mice, suggesting a possible failure to appropriately clear antigen-specific T cells after their activation. One possibility might be that antigen-activated T cells may stay in the draining lymph nodes (LNs) in plt/plt mice much longer than in control mice because of little competition for a survival niche. Another possible explanation is that CCL19 and CCL21 may participate in the priming and preparing of CD4 ϩ T cells for regulation of their response to the subsequent stimulation. Whether CCL19 and CCL21 regulate T-cell responses other than migration, such as AICD of activated T cells, is unknown. In this study, we analyzed AICD induction in CD4 ϩ T cells in plt/plt mouse in vivo and in vitro. We found that the frequency of apoptotic antigenspecific CD4 ϩ T cells was decreased in the draining LNs of plt/plt mice, when mice were subcutaneously immunized with a protein antigen in complete Freund adjuvant (CFA). Additi...