Shared and distinct roles of T peripheral helper and T follicular helper cells in human diseases

The interactions of CD4⁺ T cells and B cells are fundamental for the generation of protective antibody responses, as well as for the development of harmful autoimmune diseases. Recent studies of human tissues and blood samples have established a new subset of CD4⁺ B helper T cells named peripheral helper T (Tph) cells. Unlike T follicular helper (Tfh) cells, which interact with B cells within lymphoid organs, Tph cells provide help to B cells within inflamed tissues. Tph cells share many B helper-associated functions with Tfh cells and induce B cell differentiation toward antibody-producing cells. The differentiation mechanism is also partly shared between Tph and Tfh cells in humans, and both Tfh and Tph cells can be found within the same tissues, including cancer tissues. However, Tph cells display features distinct from those of Tfh cells, such as the expression of chemokine receptors associated with Tph cell localization within inflamed tissues and a low Bcl-6/Blimp1 ratio. Unlike that of Tfh cells, current evidence shows that the target of Tph cells is limited to memory B cells. In this review, we first summarize recent findings on human Tph cells and discuss how Tph and Tfh cells play shared and distinct roles in human diseases

〈Original Papers〉Modulation of diurnal precipitation occurrences observed in the Tibetan Plateau during monsoon season of 1998

Relations between the diurnal change of the radar echo areas and surface condition were examined at the central Tibetan Plateau during the monsoon season in 1998. During the late June, under the synoptic conditions of prevailing surface heat low with Tibetan anticyclone, a weekly time scale modulation was clearly observed in the diurnal changes of the convective activity, such as the delay of the daytime precipitation clouds toward evening, especially over the southern mountainous areas. The feature was confirmed by the diurnal weather changes indicated by multiple surface meteorological elements. Surface energy flux and hydro-meteorological measurements showed that the modulation was associated with weekly scale reducing of morning sensible heating and suppression of the planetary boundary layer development during midday. The increase of soil-surface moisture in the morning was also confirmed by the surface albedo measurements. Therefore, we hypothesize the cause of the delay of daytime precipitation by land-surface moistening due to precipitation in the previous days

Measurement of Local Plastic Deformation in Aluminum Alloy by Means of X-ray 3D Imaging Technique

AbstractTo understand the local deformation behavior is very important for improvement of deformability in aluminum alloys which possess poor deformation limit in comparison with steels. However, measurement of local deformation in the interior of metal is not sufficiently carried out. In this study, the development of local plastic strain is measured by means of X-ray 3D imaging technique, i.e. high-resolution synchrotron X-ray microtomography. The marker tracking method, which is based on 3D image processing in volumetric image, is developed for obtaining local strains in 3D. Deformation behaviour is particularly different in individual grains. It was found that grains with different orientations deform maintaining harmony by shear deformation

A Rare Case of Inflammatory Myofibroblastic Tumor of the Diaphragmatic Parietal Pleura with Dissemination

Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm that occurs at different sites in the body. Pleural IMT in particular is especially rare. IMTs infrequently tend to have malignancy. We report a rare case of advanced diaphragmatic parietal pleural IMT with dissemination. A 30-year-old woman complained of right upper abdominal pain. Computed tomography showed a large lobulated mass over the right diaphragm, but no disseminated nodules were noted. Intraoperatively, we found the primary tumor arising from the diaphragmatic parietal pleura and a dozen disseminated nodules, and we removed them completely. The histopathological and immunohistochemical diagnosis was IMT

Downregulation of CD4 is required for maintenance of viral infectivity of HIV-1

AbstractDownregulation of virus receptors on the cell surface is considered to be important in preventing superinfection. HIV-1 encodes multiple gene products, Env, Vpu, and Nef, involved in downregulation of CD4, a major HIV-1 receptor. We found that simultaneous mutations in both vpu and nef severely impaired virus replication. We examined the involvement of CD4 downregulation mediated by Vpu and Nef in the modification of virus infectivity. The mutation in vpu increased CD4 incorporation into virions without affecting the Env content in it, inhibiting the attachment step of virions to the CD4-positive cell surface. Although a single mutation in nef suppresses virus infectivity via a CD4-independent mechanism, it could augment CD4 incorporation in virions in combination with a vpu mutation. These results indicated that CD4 downregulation was necessary for maintenance of Env function in the virion

Mycophenolate mofetil for immune checkpoint inhibitor‐related hepatotoxicity relapsing during dose reduction of corticosteroid: A report of two cases and literature review

[Background] Immune checkpoint inhibitors (ICIs) sometimes cause immune-related liver injury, which can lead to cessation of treatment, hospitalization, and even mortality. Although high-dose corticosteroids are usually effective in treatment of ICI-related liver injury, one fifth of affected patients require additional immunosuppressive therapy. It remains uncertain how best to treat ICI-related liver injury that relapses under corticosteroid therapy after temporary remission. [Case] Here we report two cases of ICI-related liver injury successfully treated with mycophenolate mofetil (MMF). In the first case, a 74-year-old man with stage IIIA lung cancer underwent curative chemoradiotherapy. After the second infusion of durvalumab, grade 3 ICI-related liver injury (mixed pattern) developed. In the second case, a 46-year-old man with stage IVB lung cancer received pembrolizumab-containing chemotherapy. After the first cycle, grade 2 ICI-related hepatitis developed. In the both cases, liver injury improved with high-dose prednisolone but relapsed during tapering of the drug. After liver biopsy was performed to confirm the diagnosis of ICI-related liver injury, MMF (2000 mg/day) was added. MMF was effective for both patients and permitted discontinuation or reduction of prednisolone. [Conclusion] MMF appears to be an appropriate treatment option for ICI-related liver injury that respond to high-dose corticosteroids but relapse during steroid tapering