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The role of CD4+ and CD8+ T cells in the protective inflammatory response to a pulmonary cryptococcal infection.

Moderately virulent strains of Cryptococcus neoformans, inoculated via the trachea, cause a pulmonary infection in BALB/c mice that was gradually resolved by T lymphocyte-dependent mechanisms. The current studies, using monoclonal antibodies to deplete T cell subsets, demonstrated that CD4+ and CD8+ T cells combined to mediate a prominent pulmonary inflammatory infiltrate that included lymphocytes, macrophages, neutrophils, and eosinophils. The inflammatory response peaked 2 weeks after infection and coincided with the beginning of gradual pulmonary clearance of the infection. CD4/CD8 double d

Mechanism of Babao Dan on fluorouracil-induced bone marrow suppression and T cell immune disorder through MAPK pathway.

Babao Dan (BBD), a traditional Chinese herbal compound, has demonstrated significant antitumor effects and is clinically used as an adjuncti … ow hematopoiesis suppression. Furthermore, BBD restored the imbalance in the proportions of Th1 and Th2 cells within the spleens of 5-FU-induced mice. It also reversed the inhibition of CD25+ and CD69+ expression, the reduction in lymphocyte division generation, and the decreased expression of Ki67 and PCNA, thereby enhancing T-cell activation and prolifera …

Paradoxical Th1 activation and CTLA-4 regulation is beneficial during latent cryptococcosis.

UNLABELLED: Cryptococcus neoformans is the predominant causative agent of cryptococcal meningitis in immunocompromised individuals. Conversely in immunocompetent individuals, C. neoformans establishes a latent pulmonary infection characterized by a paucity of clinical symptoms. Using a mouse inhalation model of latent C. neoformans infection, we previously showed that CD4 T-cells are necessary for preventing fungal proliferation in the lungs. In the current study, we performed single cell RNA sequencing (scRNAseq) and found that the CD4 T-cell response was both highly heterogenous and dichotom

T Cell Subsets in Graft Versus Host Disease and Graft Versus Tumor.

Allogeneic hematopoietic cell transplantation (allo-HCT) is an essential therapeutic modality for patients with hematological malignancies and other blood disorders. Unfortunately, acute graft-versus-host disease (aGVHD) remains a major source of morbidity and mortality following allo-HCT, which limits its use in a broader spectrum of patients. Chronic graft-versus-host disease (cGVHD) also remains the most common long-term complication of allo-HCT, occurring in reportedly 30-70% of patients surviving more than 100 days. Chronic GVHD is also the leading cause of non-relapse mortality (NRM) occ

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… Regulatory T Cells in GVHD Th2 Th2 cells mainly produce IL-4, IL-5, IL-10, and IL-13 ( 113 ). GATA-binding protein 3 (GATA3) was found to be the master transcription factor for Th2 cells ( 114 ). … Tc2 cells overlap with Th2 cells in many ways, including their cytokine profile and transcription factor. However, they express both less IL-4 and GATA3 than Th2 cells ( 115 , 116 ). …

Subsets of mononuclear phagocytes are enriched in the inflamed colons of patients with IBD.

BACKGROUND: Myeloid cells, especially mononuclear phagocytes, which include monocytes, macrophages and dendritic cells (DC), play vital roles in innate immunity, and in the initiation and maintenance of adaptive immunity. While T cell-associated activation pathways and cytokines have been identified and evaluated in inflammatory bowel disease (IBD) patients (Neurath, Nat Rev Gastroenterol Hepatol 14:269-78, 1989), the role of mononuclear phagocytes are less understood. Recent reports support the crucial role of DC subsets in the development of acute colitis models (Arimura et al., Mucosal Immu

EmTIP, a T-Cell immunomodulatory protein secreted by the tapeworm Echinococcus multilocularis is important for early metacestode development.

BACKGROUND: Alveolar echinococcosis (AE), caused by the metacestode of the tapeworm Echinococcus multilocularis, is a lethal zoonosis associated with host immunomodulation. T helper cells are instrumental to control the disease in the host. Whereas Th1 cells can restrict parasite proliferation, Th2 immune responses are associated with parasite proliferation. Although the early phase of host colonization by E. multilocularis is dominated by a potentially parasitocidal Th1 immune response, the molecular basis of this response is unknown. PRINCIPAL FINDINGS: We describe EmTIP, an E. multilocular

MHC class II-dependent abnormal reactivity toward bacterial superantigens in immune cells of NOD mice.

Superantigens have been implicated in the pathogenesis of type I diabetes and other immune-mediated diseases. We therefore tested the hypothesis of an abnormal reactivity of the immune system toward bacterial superantigens during the prediabetic phase. For this purpose, splenocytes from NOD (H-2g7) mice were exposed to two well-characterized superantigens: Staphylococcal aureus enterotoxin-B (SEB) and toxic shock syndrome toxin-1 (TSST-1). Cells from BALB/c (H-2d) and C57BL/6 (H-2b) mice as well as those from NON (H-2non) and NOR (H-2g7) mice were used as controls. After 72 h of co-culture wit

Distinctive modulation by IL-4 and IL-10 of the effector function of murine thyroglobulin-primed cells in "transfer-experimental autoimmune thyroiditis".

Experimental autoimmune thyroiditis (EAT) is characterized by autoreactive T and B cell responses, a marked lymphocytic infiltration of the thyroid gland, and the occurrence of circulating autoantibodies to thyroglobulin. Direct evidence for the involvement of lymphocytes stems from the observation that EAT can be induced in naive, irradiated CBA/J mice by transfer of in vitro restimulated effector spleen cells obtained from murine thyroglobulin (mTg)-immunized donors. Using this transfer-EAT (tEAT) model, we have investigated whether addition of recombinant murine IL-4 (rIL-4) or human IL-10

The role of high-fiber diets in modulating the gut-lung axis and asthmatic inflammation.

The gut microbiota is a key regulator of human health and disease, exhibiting considerable functional diversity. High-fiber diets are known to profoundly reshape the gut microbial composition and its metabolic output, notably enhancing the production of short-chain fatty acids (SCFAs). These SCFAs mediate communication along the gut-lung axis through multiple mechanisms, including epigenetic modifications, receptor-mediated signaling, and immunomodulation. Consequently, SCFAs promote regulatory T-cell expansion, restore Th1/Th2 balance, and alleviate airway inflammation in asthma. While clinic

P2 Receptors as Therapeutic Targets in Allergic Rhinitis: Insights From the Use of Natural Products and Preclinical Studies.

Allergic rhinitis (AR) is a chronic inflammatory disorder of the upper airways that is mediated by immunoglobulin E (IgE) and triggered by environmental allergens. Current pharmacological therapies, including antihistamines, corticosteroids, and immunotherapy, offer symptomatic relief but are limited by their incomplete disease-modulating effects and potential adverse side effects. Purinergic P2 receptors (P2Rs; P2X and P2Y subtypes) have emerged as key modulators of allergic inflammation and regulate mast cell degranulation, T helper 2 (Th2) cytokine release, eosinophil recruitment, and NLRP3

Inflammation-Driven Molecular Ageing in Chronic Inflammatory Skin Diseases: Is There a Role for Biologic Therapies?

Chronic inflammatory skin diseases such as atopic dermatitis, psoriasis, and hidradenitis suppurativa are systemic conditions marked by persistent immune activation. Growing evidence links them to molecular and vascular ageing, including oxidative stress, endothelial dysfunction, and reduced expression of longevity-related proteins like Klotho and SIRT1. This narrative review examines how Th17- and Th2-driven inflammation contributes to systemic inflammageing. Key cytokines-IL-17, IL-23, IL-4, IL-13, and IL-31-promote endothelial damage, oxidative stress, and metabolic dysfunction. We highligh

Treating BCG-Induced Cystitis with Combined Chondroitin and Hyaluronic Acid Instillations in Bladder Cancer.

In non-muscle invasive bladder cancer, Bacillus Calmette-Guérin (BCG) responders benefit from strong Th1-type inflammatory and T cell responses mediating tumor rejection. However, the corresponding lack of anti-inflammatory Th2-type immunity impairs tissue repair in the bladder wall and facilitates the development of cystitis, causing urinary pain, urgency, incontinence, and frequency. Mechanistically, the leakage of the glycosaminoglycan (GAG) layer enables an influx of potassium ions, bacteria, and urine solutes towards the underlying bladder tissue, promoting chronic inflammation. Treatment

A rare case of Rhupus syndrome with Hashimoto's thyroiditis, associated adverse effect of drugs and incidental findings.

The term Rhupus is coded for the individuals who have rheumatoid like arthritis with erosions and fulfil the criteria for both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Abnormal Th2 cell plays a central role in SLE while Th1 participate in RA. Thus the overlap of SLE and RA has a very low incidence (0.01%-0.2%) in patient with arthritis. This 40-year-old male patient presented with complains of severe multiple joint pain with progressive deformities, diminished vision from last 2 months, redness on back, headache and swelling over scalp. As this patient had history of s

IgG4-related disease in asbestos-related pleural disease.

A 67-year-old man with a history of asbestos exposure and rounded atelectasis complained of cough and swelling in the left submandibular region. Computed tomography showed an increase in size of the right lower lung lobe lesion, which was recognized as the pre-existing rounded atelectasis, as well as swelling of the pancreas and submandibular glands. Biopsy from a submandibular gland and the pulmonary lesion led to a diagnosis of immunoglobulin G4-related disease (IgG4-RD). IgG4-RD is a recently recognized disease that was first reported as an autoimmune disease; however, some reports have ind

X-linked lymphoproliferative disease in an adult.

X-linked lymphoproliferative disease (XLP) is an inherited immunodeficiency characterized by an extreme susceptibility to Epstein-Barr virus (EBV) infection. Patients with XLP mainly present with the 3 clinical manifestations of fulminant infectious mononucleosis, lymphoproliferative disorder, and dysgammaglobulinemia and in rare cases have aplastic anemia and lymphocytic vasculitis. The causative gene for XLP was identified as SH2D1A/DSHP/SLAM-associated protein (SAP) in 1998, and genetic analysis has been used for the definite diagnosis of XLP. Diagnosis for most patients occurs at ages youn

Induction of hepatic pathology in SCID-Hu mice engrafted with peripheral blood lymphocytes of patients with Schistosomiasis japonica.

SCID mice were engrafted with peripheral blood lymphocytes (PBL) derived from persons currently or previously infected with Schistosoma japonicum. After immunization with soluble worm antigenic preparation, the SCID-Hu mice were analyzed for a human immune response. ELISA revealed a low titer of human antibody recognizing soluble egg antigens in 2 of 10 mice. One mouse had detectable levels of interleukin (IL)-2 and gamma-interferon, TH1 phenotype cytokines. All mice had elevated levels of IL-4, a TH2 phenotype cytokine. The human cytokine profile of the mice paralleled the patient's serum pro

Serum Soluble Fibrinogen-Like Protein 2 Estimates Increased T-Helper 2 Cytokine, Elevated Disease Severity, and Unfavorable Outcomes in Allergic Rhinitis Patients.

OBJECTIVE: Soluble fibrinogen-like protein 2 (sFGL2) may be involved in the pathology and progression of allergic rhinitis (AR) through regulating T-helper (Th)2 cell response. This study aimed to explore the ability of sFGL2 to estimate outcomes in AR patients. METHODS: sFGL2 was detected in the serum sample of 119 AR patients at baseline and 20 healthy controls (HCs) after enrollment by enzyme-linked immunosorbent assay. In AR patients, disease severity was assessed at baseline as well as 4 weeks (W4) and 8 weeks (W8) after enrollment by the total nasal symptom score (TNSS). RESULTS: sFGL2

Th2-biased immune responses to body migrating Ascaris larvae in primary infection are associated with pathology but not protection.

Helminth infections lead to an overdispersion of the parasites in humans as well as in animals. We asked whether early immune responses against migrating Ascaris larvae are responsible for the unequal distribution of worms in natural host populations and thus investigated a susceptible versus a resistant mouse strain. In mice, the roundworm larvae develop until the lung stage and thus early anti-Ascaris immune responses against the migrating larvae in the liver and lung can be deciphered. Our data show that susceptible C57BL/6 mice respond to Ascaris larval migration significantly stronger com

A GATA3 Targeting Nucleic Acid Nanocapsule for In Vivo Gene Regulation in Asthma.

Allergic asthma is one of the leading chronic lung diseases of both children and adults worldwide, resulting in significant morbidity and mortality in affected individuals. Many patients have severe asthma, which is refractory to treatment, illustrating the need for the development of new therapeutics for this disease. Herein, we describe the use of a peptide cross-linked nucleic acid nanocapsule (NAN) for the delivery of a GATA3-specific DNAzyme to immune cells, with demonstration of modulated transcriptional activity and behavior of those cells. The NAN, built from peptide cross-linked surfa

A Potential Role for IL-4 and IL-13 in an Alopecia Areata-Like Phenotype: A Clinical Perspective.

Although alopecia areata (AA) has been traditionally classified as a strictly T helper type 1-mediated process, the T helper type 2 (Th2) pathway may contribute to an AA-like phenotype in some individuals. Herein, we describe three clinical cases that support the potential role of Th2 activity through the upregulation of IL-4 and IL-13 in an AA-like phenotype.