Cross-Reactivity of T Lymphocytes Recognizing a Human Cytotoxic T-Lymphocyte Epitope within BK and JC Virus VP1 Polypeptides

A transgenic mouse model was used to identify an HLA-A*02-restricted epitope within the VP1 polypeptide of a human polyomavirus, BK virus (BKV), which is associated with polyomavirus-associated nephropathy in kidney transplant patients. Peptide stimulation of splenocytes from mice immunized with recombinant modified vaccinia virus Ankara expressing BKV VP1 resulted in expansion of cytotoxic T lymphocytes (CTLs) recognizing the sequence LLMWEAVTV corresponding to amino acid residues 108 to 116 (BKV VP1p108). These effector T-cell populations represented functional CTLs as assessed by cytotoxicity and cytokine production and were cross-reactive against antigen-presenting cells pulsed with a peptide corresponding to the previously described JC virus (JCV) VP1 homolog sequence ILMWEAVTL (JCV VP1p100) (I. J. Koralnik et al., J. Immunol. 168:499-504, 2002). A panel of 10 healthy HLA-A*02 human volunteers and two kidney transplant recipients were screened for T-cell immunity to this BK virus VP1 epitope by in vitro stimulation of their peripheral blood mononuclear cells (PBMC) with the BKV VP1p108 peptide, followed by tetramer labeling combined with simultaneous assays to detect intracellular cytokine production and degranulation. PBMC from 4/10 subjects harbored CTL populations that recognized both the BKV VP1p108 and the JCV VP1p100 peptides with comparable efficiencies as measured by tetramer binding, gamma interferon production, and degranulation. CTL responses to the JCV VP1p100 epitope have been associated with prolonged survival in progressive multifocal leukoencephalopathy patients (R. A. Du Pasquier et al., Brain 127:1970-1978, 2004; I. J. Koralnik et al., J. Immunol. 168:499-504, 2002). Given that both human polyomaviruses are resident in a high proportion of healthy individuals and that coinfection occurs (W. A. Knowles et al., J. Med. Virol. 71:115-123, 2003), our findings suggest a reinterpretation of this protective T-cell immunity, suggesting that the same VP1 epitope is recognized in HLA-A*02 persons in response to either BK or JC virus infection

STAT3 inhibition is a therapeutic strategy for ABC-like diffuse large B-cell lymphoma

Persistent STAT3 signaling contributes to malignant progression in many diverse types of human cancer. STAT3 is constitutively active in activated B-cell (ABC)-like diffuse large B-cell lymphomas (DLBCL), a class of nongerminal center derived DLBCL cells for which existing therapy is weakly effective. In this report, we provide a preclinical proof of concept that STAT3 is an effective molecular target for ABC-like DLBCL therapy. Direct inhibition of STAT3 with short hairpin RNA suppressed the growth of human ABC-like DLBCL in mouse models in a manner associated with apoptosis, repression of STAT3 target genes, and inhibition of a tumor-promoting microenvironment. Together, these results suggest that STAT3 is essential to maintain the pathophysiology of ABC-like DLBCL and therefore that STAT3 inhibition may offer a promising approach in its therapy. ©2011 AACR

STAT3 Inhibition Is a Therapeutic Strategy for ABC-like Diffuse Large B-Cell Lymphoma

Persistent STAT3 signaling contributes to malignant progression in many diverse types of human cancer. STAT3 is constitutively active in activated B cell (ABC)-like diffuse large B cell lymphomas (DLBCL), a class of non-germinal center derived DLBCL cells for which existing therapy is weakly effective. In this report, we provide a preclinical proof of concept that STAT3 is an effective molecular target for ABC-like DLBCL therapy. Direct inhibition of STAT3 with shRNA suppressed the growth of human ABC-like DLBCL in mouse models in a manner associated with apoptosis, repression of STAT3 target genes and inhibition of a tumor-promoting microenvironment. Together, these results suggest that STAT3 is essential to maintain the pathophysiology of ABC-like DLBCL and therefore that STAT3 inhibition may offer a promising approach in its therapy

DataSheet_1_Plasmodium curtails autoimmune nephritis via lasting bone marrow alterations, independent of hemozoin accumulation.pdf

The host response against infection with Plasmodium commonly raises self-reactivity as a side effect, and antibody deposition in kidney has been cited as a possible cause of kidney injury during severe malaria. In contrast, animal models show that infection with the parasite confers long-term protection from lethal lupus nephritis initiated by autoantibody deposition in kidney. We have limited knowledge of the factors that make parasite infection more likely to induce kidney damage in humans, or the mechanisms underlying protection from autoimmune nephritis in animal models. Our experiments with the autoimmune-prone FcγR2B[KO] mice have shown that a prior infection with P. yoelii 17XNL protects from end-stage nephritis for a year, even when overall autoreactivity and systemic inflammation are maintained at high levels. In this report we evaluate post-infection alterations, such as hemozoin accumulation and compensatory changes in immune cells, and their potential role in the kidney-specific protective effect by Plasmodium. We ruled out the role of pigment accumulation with the use of a hemozoin-restricted P. berghei ANKA parasite, which induced a self-resolved infection that protected from autoimmune nephritis with the same mechanism as parasitic infections that accumulated normal levels of hemozoin. In contrast, adoptive transfer experiments revealed that bone marrow cells were altered by the infection and could transmit the kidney protective effect to a new host. While changes in the frequency of bone marrow cell populations after infection were variable and unique to a particular parasite strain, we detected a sustained bias in cytokine/chemokine expression that suggested lower fibrotic potential and higher Th1 bias likely affecting multiple cell populations. Sustained changes in bone marrow cell activation profile could have repercussions in immune responses long after the infection was cleared.</p

Научные журналы по библиотековедению, библиографоведению и книговедению: история, реалии, перспективы

The article presents the presentations of the participants of the round table “Scientific Journals on Library Science, Bibliography Science and Book Studies: History, Realities, Prospects (to the 70th anniversary of the journal “Bibliotekovedenie” (Library Science)”, which took place on April 19, 2022 within the framework of the International Scientific and Practical Conference “Rumyantsev Readings — 2022”. The paper reflects the place and role of the professional scientific journals in the development of communications that contribute to the preservation of libraries as cultural heritage institutions and form the human capital and cultural potential of all generations of Russian citizens.The journal “Library Science”, established in 1952, became the nationwide scientific periodical of the library sector. Participants described in their speeches the characteristics of the publication activity of some Russian journals, professional periodicals of Belarus, Kazakhstan, Azerbaijan and the international scientific journal “Libri”. The authors highlighted the peculiarities of the creation of periodicals of the designated subject, their functioning, the management models used, the diversity of elements of publication policy and design: regional differences, typological characteristics of the founders, departmental affiliation, cultural traditions, the uniqueness of the historical conditions of creation, etc.The discussion resulted in unanimous recognition of the significant role of professional scientific periodicals in supporting the scientific infrastructure of libraries and providing methodological support of the sector, including research practices, as well as atmosphere of creativity and creative competencies. In the future, the journals are considered as points of growth of professional knowledge, interdisciplinary thinking and cultural communications, activators of the socio-cultural space.Представлены выступления участников круглого стола «Научные журналы по библиотековедению, библиографоведению и книговедению: история, реалии, перспективы (к 70-летию журнала “Библиотековедение”)», который состоялся 19 апреля 2022 г. в рамках Международной научно-практической конференции «Румянцевские чтения — 2022». Отражены место и роль профессиональных научных журналов в развитии коммуникаций, способствующих сохранению библиотек как учреждений культурного наследия и формирующих человеческий капитал и культурный потенциал всех поколений граждан России.Журнал «Библиотековедение», созданный в 1952 г., стал общенациональным научным периодическим изданием библиотечной отрасли, задачи которого в разные периоды фокусировались на проблемах становления библиотек как активных участников процессов, происходящих в обществе, и их отражении в научных исследованиях. «Библиотековедение» остается признанным и наиболее авторитетным журналом.В выступлениях участников были отмечены характеристики публикационной активности некоторых российских журналов, профессиональной периодики Беларуси, Казахстана, Азербайджана и международного научного журнала Libri.Выделены особенности создания периодических изданий обозначенной тематики, их функционирования, используемых управленческих моделей, разнообразие элементов публикационной политики и оформления: региональные различия, типологические характеристики учредителей, ведомственная принадлежность, культурные традиции, уникальность исторических условий создания и др.Итогом обсуждения стало единодушное признание значимой роли профессиональной научной периодики в поддержке научной инфраструктуры библиотек и методического обеспечения отрасли, включая исследовательские практики, атмосферу творчества и креативных компетенций. В перспективе журналы рассматриваются как точки роста профессиональных знаний, междисциплинарного мышления и культурных коммуникаций, активаторы социокультурного пространства