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Skin exudate levels of interleukin 6, interleukin 1 and other cytokines in mycosis fungoides.

The role of locally released cytokines in inducing lymphocyte activation and infiltration in the skin lesions of mycosis fungoides has been investigated. The levels of selected cytokines were measured in chamber fluid samples from lesional and control skin. Biologically active interleukin 6 was significantly elevated in lesional samples and a recombinant form of this cytokine was shown to induce lymphocyte migration in an in vitro assay. Biologically active interleukin 1 was detected in all control chamber fluid samples. Significantly reduced levels of this cytokine were present in lesional sa…

Associations of adiposity, atherogenic lipid phenotypes, systemic immune-inflammatory indices, and vascular aging markers with depression in US adults: NHANES 2005-2020.

The biological mechanisms linking cardiometabolic health, immune-inflammatory activation, and vascular aging with depression remain incompletely understood. We aimed to examine the associations of body mass index (BMI), atherogenic lipid phenotypes, systemic immune-inflammatory indices, and vascular aging markers with the risk of moderate-to-severe depression among US adults. We analyzed data from 17,011 participants in the National Health and Nutrition Examination Survey (NHANES) 2005-2020. Depression was defined as a Patient Health Questionnaire-9 score ≥ 10. Independent predictors included

Selective blocking of voltage-gated K+ channels improves experimental autoimmune encephalomyelitis and inhibits T cell activation.

Kaliotoxin (KTX), a blocker of voltage-gated potassium channels (Kv), is highly selective for Kv1.1 and Kv1.3. First, Kv1.3 is expressed by T lymphocytes. Blockers of Kv1.3 inhibit T lymphocyte activation. Second, Kv1.1 is found in paranodal regions of axons in the central nervous system. Kv blockers improve the impaired neuronal conduction of demyelinated axons in vitro and potentiate the synaptic transmission. Therefore, we investigated the therapeutic properties of KTX via its immunosuppressive and symptomatic neurological effects, using experimental autoimmune encephalomyelitis (EAE), an a…

Suppression of human lymphocyte responses by oral spirochetes: a monocyte-dependent phenomenon.

Spirochetes have been implicated in the pathogenesis of several human infections including syphilis, yaws, Lyme disease, and periodontal dis … y. In contrast, sonicates of T. vincentii (medium-sized spirochetes) had no demonstrable effects on lymphocyte activation. The suppressive factor derived from T. denticola is heat-labile with a m.w. of approximately 100,000. To achieve maximal suppression, sonicates had to be added during the first 24 hr of incubation; there was no inhibition observed when added at 48 …

Mechanoluminescence: lymphocyte analysis after exposure to ionizing radiation.

Lymphocyte mechanoluminescence (ML) develops as a result of mechanochemical activation of cells. This paper describes devices (tribogenerators) and techniques for lymphocyte mechanoluminescence analysis. At different stages of the cellular cycle the ML of non-irradiated peripheral blood lymphocytes (PBL) showed characteristic differences. After (60)Co gamma -irradiation of PBL in vitro at 0.25 Gy and 1 Gy an alteration of ML was observed with a relationship between ML values of lymphocytes, and also of mitochondria (MT), and the dose of ionizing radiation used. By using bioluminescence techniq

IgA natural antibodies are produced following T-cell independent B-cell activation following stroke.

Up to 30% of stroke patients experience cognitive decline within one year of their stroke. There are currently no FDA-approved drugs that can prevent post-stroke cognitive decline, in part due to a poor understanding of the mechanisms involved. We have previously demonstrated that a B-lymphocyte response to stroke, marked by IgA + cells, can cause delayed cognitive dysfunction in mice and that a similar adaptive immune response occurs in the brains of some human stroke patients that suffer from vascular dementia. The stimuli which trigger B-lymphocyte activation following stroke, and their tar…

A monoclonal antibody that blocks poliovirus attachment recognizes the lymphocyte homing receptor CD44.

A monoclonal antibody, AF3, was previously shown to specifically inhibit poliovirus binding to HeLa cells and to detect a 100-kDa glycoprote … c cells. Anti-CD44 monoclonal antibodies, previously reported to induce CD44-mediated modulation of lymphocyte activation and adhesion, compete with 125I-AF3 in binding assays, demonstrating functional overlap among the epitopes. The anti-CD44 monoclonal antibody A3D8, which binds to a greater molecular weight range of CD44 than does AF3, inhibits poliovirus binding to …

Circadian clocks and adaptive immune function: from mechanisms to therapeutic applications.

The circadian clock exerts profound regulatory control over adaptive immunity, particularly affecting T and B lymphocyte development, trafficking, activation, and effector function. These immune cells possess autonomous molecular clocks governed by core genes such as Bmal1, Clock, Per1/2, and Cry1/2, which influence transcriptional programs related to receptor expression, cytokine signaling, and metabolism. Circadian regulation shapes the daily oscillation of lymphocyte recirculation through lymphoid organs, modulates antigen responsiveness, and fine-tunes subset differentiation-most notably s

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… In many cancers, the tumor microenvironment shows dysregulated expression of immune-checkpoint molecules, including Programmed cell death protein 1 (PD-1), Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4), T-cell Immunoglobulin and Mucin-domain containing-3 (TIM-3), and Lymphocyte Activation Gene-3 (LAG-3) …

Epstein-Barr virus (EBV) latent membrane protein 2A regulates B-cell receptor-induced apoptosis and EBV reactivation through tyrosine phosphorylation.

Epstein-Barr virus (EBV) is a human herpesvirus that establishes a lifelong latent infection of B cells. Within the immune system, apoptosis is a central mechanism in normal lymphocyte homeostasis both during early lymphocyte development and in response to antigenic stimuli. In this study, we found that latent membrane protein 2A (LMP2A) inhibited B-cell receptor (BCR)-induced apoptosis in Burkitt's lymphoma cell lines. Genistein, a specific inhibitor of tyrosine-specific protein kinases, blocked BCR-induced apoptosis and EBV reactivation in the cells. These findings indicate that LMP2A blocks

Distribution of Gc protein (vitamin D binding protein) on the surfaces of normal human lymphocytes and leukemic lymphocytes.

Distribution of membrane-bound Gc protein (mGc) in normal lymphocyte subpopulations and leukemic lymphocytes was studied using a rabbit antiserum specific to Gc protein. Forty to fifty percent of the normal peripheral blood mononuclear cells were stained with anti-Gc antiserum by membrane immunofluorescence, and almost all of the B cells (B1+) and NK cells (Leu 11+) were mGc-positive. Only a few resting T cells (T3+) reacted with anti-Gc, but mGc appeared in a significant number of the T cells after activation by PHA. The distribution of mGc on leukemic lymphocytes of various types nearly corr

Activation of nuclear factor of activated T cells by human T-lymphotropic virus type 1 accessory protein p12(I).

Human T-lymphotropic virus type 1 (HTLV-1) is the agent of an aggressive malignancy of CD4(+) T lymphocytes, called adult T-cell lymphoma/leukemia, and is associated with numerous immune-mediated diseases. To establish infection, HTLV-1 must activate targeted T cells during early stages of infection. We recently demonstrated that the HTLV-1 accessory protein p12(I) is critical for persistent infection in vivo and for viral infectivity in quiescent primary lymphocytes, suggesting a role for p12(I) in lymphocyte activation. To test whether p12(I) modulates signaling pathways required for T-lymph…

Multiple myeloma and the potential of new checkpoint inhibitors for immunotherapy.

Multiple myeloma (MM), a cancer of the bone marrow, is categorized as the second most common hematological malignancy of adults in the Weste … immunoreceptor with Ig and ITIM domains (TIGIT), T-cell immunoglobulin, and mucin domain 3 (Tim-3), lymphocyte activation gene-3 (LAG-3), V-domain Ig Suppressor of T-cell activation and killer immunoglobulin-like receptors along with bispecific T-cell antibodies (BsAbs) will be discussed. Further, we summarized the underlying biology of these checkpoints in cancer and …

Mutations in the genes coding for the NF-κB regulating factors IκBα and A20 are uncommon in nodular lymphocyte-predominant Hodgkin's lymphoma.

Nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL) shows constitutive NF-kappaB activity in the malignant lymphocyte-predominant (LP) cells. Constitutive NF-kappaB activity also plays a central pathogenetic role in classical Hodgkin's lymphoma (cHL), where inactivating mutations in the NFKBIA and TNFAIP3 genes, coding for the negative NF-kappaB regulators IkappaBalpha and A20, respectively, contribute to NF-kappaB activation. To determine whether mutations in NFKBIA and TNFAIP3 are also involved in the pathogenesis of NLPHL these genes were sequenced from microdissected LP cells of 10 p

Different circulating lymphocyte profiles in patients with different subtypes of juvenile idiopathic arthritis.

OBJECTIVE: To determine the immunophenotypic profiles of circulating lymphocytes in patients with different disease types of Juvenile Idiopathic Arthritis (JIA). METHODS: Peripheral blood lymphocyte subsets from 19 patients with oligoarticular JIA (o-JIA), 10 patients with polyarticular JIA (p-JIA), 12 patients with systemic JIA (s-JlA) andfrom 41 age-matched healthy controls were characterized by two color immunofluorescence flow cytometry analysis. RESULTS: Patients with o-JIA and p-JIA had increased numbers of HLA-DR+ Tcells and Tcells co-expressing CD57 and CD16/56, indicating T cell act

[The expression of lymphopoietic differentiation antigens on the membrane of the peripheral blood mononuclear cells in lymphosarcoma tumor progression].

Monoclonal antibodies were used in the indirect immunofluorescence test to assay the antigenic features of lymphoid cells in patients with lymphosarcoma. Some patients with progression of lymphoblastic lymphoma showed an increased content of T lymphocyte expressing early activation antigens, antigens of early hemopoietic progenitors, and CALLA-antigens.

The lymphocyte transformation test in allergic contact dermatitis: New opportunities.

Allergic contact dermatitis (ACD) is driven by the activation and proliferation of allergen-specific memory T-lymphocytes and is currently diagnosed by patch testing with a selected panel of chemical allergens. The lymphocyte transformation test (LTT) can be used to monitor ex vivo T-lymphocyte responses to antigens, including contact allergens. The LTT is not viewed as being an alternative to patch testing, but it does seek to reflect experimentally skin sensitization to specific chemicals. The LTT is based on stimulation in vitro of antigen-driven T-lymphocyte proliferation. That is, exposur

In vitro lymphocyte proliferation induced by radio-frequency electromagnetic radiation under isothermal conditions.

Whole human blood was exposed or sham-exposed in vitro for 2 h to 27 or 2,450 MHz radio-frequency electromagnetic (RF) radiation under isoth … on lymphocyte morphology or viability. Notwithstanding the characteristic temperature dependence of lymphocyte activation in vitro, the isothermal exposure conditions of this study warrant the conclusion that the biphasic, dose-dependent effects of the radiation on lymphocyte proliferation were not dependent on heating.

Age but not sex modifies lymphoid immune responses in murine sepsis.

Sepsis disproportionately affects the elderly, and the cellular mechanisms driving age- and sex-dependent lymphoid immune remodeling remain poorly defined. In this work, we mapped the splenic lymphoid transcriptional landscape of young and older adult, male and female mice after sepsis by single-cell RNA sequencing. While both sexual and age dimorphism shaped the baseline lymphocyte composition, the transcriptional reprogramming induced by sepsis was significantly influenced only by age. Sepsis induced a proportional reduction in lymphocytes across age and sex groups; however, aging modified t

Targeting Periodontitis with Treg-Derived Extracellular Vesicles: Modulation of Macrophages and CD8+ T-Cell Responses.

Periodontitis is a chronic inflammatory disease characterized by alveolar bone loss driven by dysregulated immune responses. We previously showed that extracellular vesicles derived from retinoic acid-induced regulatory T lymphocytes (RA-Treg EVs) suppress pathogenic CD4+ T-lymphocyte responses and reduce alveolar bone loss during periodontitis. Herein, we investigated whether RA-Treg EVs also modulate macrophage and CD8+ T-lymphocyte responses during experimental periodontitis. Ligature-induced periodontitis was generated in mice, followed by local administration of RA-Treg EVs. Alveolar bone

The role of mTOR-mediated signaling in the regulation of cellular migration.

Mechanistic target for rapamycin (mTOR) is a serine/threonine protein kinase that forms two distinct complexes mTORC1 and mTORC2, integrating mitogen and nutrient signals to regulate cell survival and proliferation; processes which are commonly deregulated in human cancers. mTORC1 and mTORC2 have divergent molecular associations and cellular functions: mTORC1 regulates in mRNA translation and protein synthesis, while mTORC2 is involved in the regulation of cellular survival and metabolism. Through AKT phosphorylation/activation, mTORC2 has also been reported to regulate cell migration. Recent