HTLV-1-infected T-cell lines suppress IgG and autoantibody production from B cells of healthy donors and patients with Sjögren's syndrome through cell-to-cell contact and some humoral factors.

This study established a 21-day in vitro culture system for human long-lived plasma cells (LLPCs), demonstrating their survival and antibody secretion depend on stromal cell contact. PI3K and NF-kappaB pathways were crucial for LLPC survival, aligning with findings in mice. This model advances the understanding of human LLPC biology.

This review addresses how fibroblastic reticular cells (FRCs) undergo metabolic reprogramming in response to infections, autoimmune diseases, and cancer, adjusting their glycolysis, oxidative phosphorylation, and fatty acid metabolism to modulate immune functions. These metabolic shifts in FRCs highlight potential therapeutic strategies to improve immune regulation across various disease contexts.

Depending on whether the interactions occur in vitro or in vivo, physical binding between two B cells with complementary BCRs leads to distinct outcomes for the participating cells. In vitro, both the Id⁺ B cell and the complementary anti-idiotypic B cell undergo apoptosis. In vivo, follicular αId B cells expand, whereas marginal zone Id⁺ B cells become deleted.

We here provide detailed protocols for isolating single cell suspension from human nonlymphoid tissues, such as gingiva, lung, intestine, skin, and different tumor tissues as well as tumor-draining lymph nodes. Further, we provide gating strategies for flow cytometric analysis of human DC subpopulations in diverse nonlymphoid tissues.

After exposure to LPS, Alveolar macrophages (AMs) secrete TNF-α to induce GM-CSF production by alveolar epithelial cells (AECs). GM-CSF promotes AMs to secrete IL-6 and primes AMs for subsequent challenges. These results show that in response to MAMP stimulation, AMs and AECs respond collaboratively and AMs are primed.

Licensing of MSCs with MIF requires CXCR4 receptor binding. Enhanced VEGF production by MIF-licensed MSCs promotes wound healing in vitro and can be blocked using the VEGFR2 inhibitor SU-5416. MIF-licensed MSC conditioned medium significantly reduced goblet cell hyperplasia in house dust mite-driven allergic airway inflammation in vivo.

In the steady state, naïve CD4 T cells can develop into memory phenotype (MP) cells. We discovered that MP T cells include a subpopulation of Tfh cells. MP Tfh cells share key markers with pathogen-induced memory Tfh cells and can support germinal center formation and antibody responses to infection.

Neutrophil extracellular traps (NETs) contribute to SLE development, yet their interaction with Regulatory T cells (Tregs) remains obscure. This study reveals that selectively enhanced NETs in mice suppress Treg production and function. Through modulating naive CD4⁺ T cells via TLR4, NETs inhibit Treg differentiation, bridging innate and adaptive immune responses.

Multimodal single-cell RNA sequencing identified a population of CD8+ T cells elevated in tumor tissue enriched for interferon-stimulated genes (ISG). These ISG cells are clonally related to a population of Granzyme K (GZMK)-expressing CD8⁺ T cells. However, unlike GZMK-expressing T cells, ISG cells were transcriptionally inert in response to in vitro stimulation. Created in BioRender.com

Thymic NC-derived mesenchymal cells produce factors, including Flt3L and Periostin, after irradiation. Depletion of NC-derived mesenchyme reduces these factors, decreases the abundance of ETPs, and impairs thymic reconstitution postirradiation. The addition of Flt3L and Periostin after NC-derived mesenchyme depletion restores reconstitution, highlighting the importance of NC-derived mesenchyme in thymus regeneration.

This study investigates the microbiome as a potential factor underlying the apparent differences in immune stimulation required for HLH induction in perforin-deficient mice compared to FHL-2 patients. Using PKO-Wildlings, we show that while immune activation by natural microbiota is not sufficient to induce HLH, it can influence manifestations of LCMV-induced disease.

Working on the 1000-donor Milieu Interieur cohort with ex vivo whole blood stimulation, we demonstrate that naturally occurring cytokine autoantibodies (c-aAb) in healthy donors can neutralize cytokine availability and regulate proinflammatory gene expression.

The role of CD4⁺ T cells in promoting cellular and humoral immunity induced by novel mRNA–LNP and adenovirus vector vaccine technologies is incompletely understood. Surprisingly, we identified a discordant need for CD4⁺ T cell help based on both vaccine platform and arm of adaptive immunity examined. These data provide further evidence of the unique biology underpinning these new technologies.

Human CD8αβ was produced as an Fc-fusion via knob-in-hole mediated heterodimerization and bound class I pHLA and MR1 with similar affinity to human CD8αα, but did not bind CD1a, b, c, or d. An inverse relationship between CD8:pHLA affinity and TCR:pHLA was observed for several alleles.

Diversification of transgenic TCRs by CRISPR/Cas9-mediated mutagenesis of Tcra and Tcrb chain genes in vivo converts monoclonal repertoires of known specificity into an oligoclonal pool of TCRs of altered antigen reactivities. This generally applicable approach helps to identify crucial amino acid residues in the CDR3 regions required for antigen recognition.

Il1r2 deficiency in monocytes dysregulates their trafficking to inflamed tissues through increased production of the monocyte chemoattractant CCL2.

This review provides deeper insights into the localization of intra-tumoral γδ T lymphocytes in solid tumors. Additionally, a pro- or anti-tumoral influence of the tumor microenvironment and expression of checkpoint inhibitory molecules on γδ T cell functionality is described. To overcome the suppression of tumor-infiltrating γδ T cells, future immunotherapy approaches are summarized.

TSLP and its receptors CRLF2 and IL7Rα were investigated in non-COPD and COPD airways. At steady-state, TSLP is detected at low levels in bronchi and bronchioles and may contribute to inflammatory mediators’ regulation.

SARS-CoV-2 placentitis and chronic histiocytic intervillositis are associated with massive infiltration of myeloid cells and T cell activation limited to the placental intervillous space, and not in villi or decidual areas. The prominently reduced expression of apoptosis-related proteins in SARS-CoV-2 placentitis could be related to more acute and severe outcomes.

Directly ex-vivo and after fixation, autoreactive B cells were detected using fluorescent streptavidin molecules conjugated to citrullinated or arginine peptides. Anti-tetanus toxoid B cells served as controls and were detected using fluorescently labeled tetanus toxin. Antigen-specific phosphoflow revealed increased levels of pSYK, pBTK, pAKT, and pS6 in autoreactive B cells.

The anti-P2X7 monoclonal antibody (clone L4) mediates complement-dependent cytotoxicity of human leukocytes. This process preferentially targets leukocytes with high cell surface P2X7, such as monocytes and dendritic cells, presenting a new strategy to reduce P2X7 immune functions.