Open research questions in T-cell and B-cell Immunology
511 gap statements mined from T-cell and B-cell Immunology papers in our 7.9M-paper local library, which holds 2,233 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.
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What the literature leaves open
The mechanisms of Treg dysfunction in autoimmune diseases are not fully understood. Current therapeutic strategies have limitations, such as systemic immunosuppressive risks and inadequate targeting of inflamed tissues. There is a need for novel therapeutic approaches to restore Treg function and promote immune tolerance.
Regulatory T cell dysfunction and therapeutic advances in rheumatoid arthritis, psoriasis, vitiligo, and systemic lupus erythematosus · 2026 · DOIThe developmental requirements of atypical cTEC are not well understood. The properties of atypical cTEC and their role in thymus function are not clearly defined.
The alarmin IL33 marks a thymocyte dependent shift in the makeup of cortical thymic epithelial cells · 2026 · DOIThe need for a nuanced understanding of Treg biology to achieve disease-specific effects. The requirement for therapeutic strategies that can selectively enhance or impair Treg function. The importance of recognizing the dynamic phenotypic and functional shifts Tregs undergo across different compartments.
The dual role of skin-resident Tregs: balancing autoimmunity in vitiligo and immune evasion in melanoma · 2026 · DOIThe pathogenesis of most immune-mediated diseases is not yet known. There is a need for improved diagnostics and targeted therapies. The current success in dividing immune-mediated diseases into distinct clusters is significant progress.
The need to evaluate the potential of BCMA as a biomarker and therapeutic target in SLE.
B-Cell Maturation Antigen (BCMA) as a Biomarker and Potential Treatment Target in Systemic Lupus Erythematosus · 2024 · DOIThe gut microbiota contributes to autoimmune disease, yet how systemic autoimmunity reshapes microbiota-reactive CD4 T cell responses and how these cells influence disease progression remain poorly understood.
Previous studies have linked microbiota-reactive T cells and lupus-associated pathobionts to disease pathogenesis, but the pathways that regulate the accumulation, differentiation, and pathogenicity of microbiota-reactive T cells during autoimmunity remain unclear.
Yet, sex-specific factors that drive autoimmune predisposition in females remain poorly understood.
However, how these distinct, differentiated T cell populations calibrate their responsiveness remains poorly understood.
HDAC5 tunes effector competence in differentiated human CD8+ T cells through an ACTL6A-IRF4 axis · 2026 · DOIHowever, it remains unclear whether individual human LNs within and across drainage regions maintain systematically distinct repertoires, given that memory accumulates over decades of antigen exposure.
CD8+ T cells are increasingly recognized as components of the healthy brain, yet whether their specialized functional characteristics are conserved across species and how the brain microenvironment regulates their effector programs remain poorly understood.
Conserved Brain-Associated CD8+ T Cell Programs and Their Regulation by the Brain Microenvironment · 2026 · DOIGPR15 is a colon homing receptor, but its pattern of expression among gut intestinal intraepithelial lymphocytes and its role on intestinal intraepithelial lymphocyte (IEL) and epithelial homeostasis, as well as systemic metabolism and hormones remain unknown.
GPR15-GPR15L axis controls colon natural TCRαβ cells residency and enteroendocrine cell homeostasis to calibrate metabolism · 2026 · DOIThe oral cavity is a critical mucosal barrier frequently exposed to viral pathogens; however, the phenotypic characteristics and spatial organization of virus-specific T cells in the human oral mucosa remain poorly understood.
However, the mechanisms that apply to corneal epithelial (outer surface) antigens remain unknown.
Butyrophilin 3A3 (BTN3A3) senses mevalonate-derived phosphoantigens (pAgs), but its ligand chemistry remains unexplored.
AIRE induces promiscuous gene expression in mTECs, but little is known about the regulatory mechanisms of AIRE.
The autoimmune regulator (AIRE) is a target of the E3-Ubiquitin ligase Seven-in-absentia homolog 1 (SIAH1). · 2026 · DOIRegulatory T cells (T reg cells) maintain immune tolerance, but how broadly acting epigenetic pathways are selectively used by T reg cells versus conventional T cells (T conv cells) remains unclear.
Wdr82-COMPASS coordinates Foxp3 and TCR signaling to sustain T reg cell control of microbiota-driven intestinal inflammation · 2026 · DOIHowever, their subsequent maintenance remains unclear, including the involvement of the gut microbiota.
Gut microbiota contributes to the maintenance of sublingually induced regulatory T cells and tolerance in mice · 2025 · DOIPhenotypic and functional heterogeneity within the Treg lineage has been appreciated, but the etiology and impact of Treg plasticity across disease states remain incompletely understood.
OMIP‐118 : A 38‐Marker Spectral Flow Cytometry Panel to Assess Human Regulatory T Cell Phenotype and Lineage Plasticity · 2025 · DOINevertheless, whether obesity affects cDC1/Treg pathways and the generation of food tolerance remains poorly understood.
Investigating the mechanisms of Treg dysfunction in autoimmune diseases, - Developing strategies to enhance Treg function and stability, - Exploring the potential of CAR-Treg cells in treating autoimmune diseases, - Evaluating the efficacy of IL-2-Fc mutant in patients…
Regulatory T cell dysfunction and therapeutic advances in rheumatoid arthritis, psoriasis, vitiligo, and systemic lupus erythematosus · 2026 · DOIGain a full understanding of the precursor-product relationships that determine cTEC heterogeneity, - Understand the functional relevance of adult cTEC heterogeneity, and atypical IL33-expressing cTEC in particular, - Examine the scenarios in which both cTEC and mesenchyme may influence thymus regeneration via IL33…
The alarmin IL33 marks a thymocyte dependent shift in the makeup of cortical thymic epithelial cells · 2026 · DOIUnderstanding the mechanistic parallels and divergences between Treg roles in vitiligo and melanoma - Developing disease-specific therapeutic strategies - Investigating the potential of Treg-based therapies to achieve disease-specific effects while avoiding systemic immune…
The dual role of skin-resident Tregs: balancing autoimmunity in vitiligo and immune evasion in melanoma · 2026 · DOIPoorly resolved T-cell-specific functions for most helicase paralogs. Obscure molecular underpinnings of their non-canonical activities. Challenges in achieving isoform-selective pharmacological targeting.
Investigate the effects of targeting BCMA on SLE disease activity and progression, - Evaluate the potential of BCMA as a biomarker for SLE diagnosis and monitoring, - Investigate the relationship between BCMA expression and other immune cell subsets…
B-Cell Maturation Antigen (BCMA) as a Biomarker and Potential Treatment Target in Systemic Lupus Erythematosus · 2024 · DOI
Most-cited papers in T-cell and B-cell Immunology
- Control of Regulatory T Cell Development by the Transcription Factor Foxp3 · Science · 2003 · 6,624 citations
- Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells · Nature · 2006 · 5,749 citations
- Two subsets of memory T lymphocytes with distinct homing potentials and effector functions · Nature · 1999 · 4,733 citations
- Restoring function in exhausted CD8 T cells during chronic viral infection · Nature · 2005 · 3,390 citations
- Functional diversity of helper T lymphocytes · Nature · 1996 · 3,208 citations
- Phenotypic Analysis of Antigen-Specific T Lymphocytes · Science · 1996 · 2,746 citations
- A CD4+T-cell subset inhibits antigen-specific T-cell responses and prevents colitis · Nature · 1997 · 2,677 citations
- CTLA-4 Control over Foxp3 + Regulatory T Cell Function · Science · 2008 · 2,590 citations
- The Immunological Synapse: A Molecular Machine Controlling T Cell Activation · Science · 1999 · 2,519 citations
- B cells and tertiary lymphoid structures promote immunotherapy response · Nature · 2020 · 2,477 citations
Most recent work
- T cell homing and exercise · PubMed · 2026
- Next steps in regulatory T cells: Biology and clinical application · Cell · 2026
- T cell adaptation in chronic infections and tumors · Cellular and Molecular Immunology · 2026
- B cells drive CD4 T cell immunosenescence and age-associated health decline · Science Immunology · 2026
- Cytotoxic CD4+ T cells: origin, biological functions, diseases and therapeutic targets · Signal Transduction and Targeted Therapy · 2026
- Immune signatures of common exposures through co-occurrence of T-cell receptors in tens of thousands of donors · bioRxiv · 2026
- Local antibody feedback enforces a checkpoint on affinity maturation in the germinal center and promotes epitope spreading · Immunity · 2026
- Antibody-mediated feedback modulates interclonal competition in the germinal center · Immunity · 2026
- Metabolic quiescence of naive-like memory T cells precedes and maintains antigen-specific T cell memory · Nature Immunology · 2026
- The TCR and LCK: foundations for T-cell activation and therapeutic innovation · Frontiers in Immunology · 2026
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