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Immune factors are important antecedents in the pathophysiology of necrotizing enterocolitis (NEC). However, studies on the peripheral blood lymphocyte subsets changes in NEC patients among different Bell stages and in patients requiring surgery are scarce. 34 infants with NEC and 33 age-matched controls were included. Peripheral blood was collected within 48 h after NEC diagnosis. Peripheral blood B and T lymphocytes subsets were detected by 12-color flow cytometry. Cell ratios were calculated, and their relationship to disease severity and their roles as indicators for surgery were assessed. NEC patients showed elevated percentages of unSwB cells (CD27+IgD+ unswitched memory/activated B cells)/B cells, SwB cells (CD27+IgD-switched memory B cells)/B cells, CD8+ T (CD3+CD8+ T cells)/T cells, Tem (CD45RA-CCR7-effector memory T cells)/CD4+ T cells, Tem/CD8+ T cells and decreased Bn (CD27-IgD+ naïve B cells)/B cells, CD4+T (CD3+CD4+ T cells)/T cells, CD45RA+ CCR7+ naïve T cells (CD45RA+CCR7+ naïve T cells)/CD8+T cells. Compared to NEC patients at BELL stage I + II, patients at BELL stage III showed increased percentages of SwB cells/B cells, antibody secreting cell (ASC, CD3-CD20-CD27high CD38high ASCs)/B cells and Tem/CD4+ T cells, and decreased percentages of CD45RA+CCR7+ naïve T cells/CD4+ T cells. The Receiver Operating Characteristic Curve analysis showed that the sensitivity of ASC/B cells ratio (0.52%) is 86.67% and the specificity of Tem/CD4+T ratio (5.22%) is 100%, indicating that NEC patients required surgery. The severity of NEC exhibits codirectional changes with the maturation of B and T lymphocytes, especially CD4+ T cells. The increased ASC/B and Tem/CD4+ T cells could serve as potential indicators for NEC patients requiring surgery. [ABSTRACT FROM AUTHOR]

The autoimmune/inflammatory disorder psoriasis is characterized by keratinocyte proliferation and immune cell infiltration of the skin. TCR + CD3 + CD4 − CD8 − “double negative” (DN) T cells can derive from CD8 + T cells through the down-regulation of CD8. The inhibitory molecule programmed death (PD-)1 is expressed on activated T cells and plays a role in the maintenance of peripheral tolerance. A subset of DN T cells, characterized by the expression of PD-1, has recently been demonstrated to be self-reactive. We demonstrate that a majority of DN T cells exhibits effector memory phenotypes, express IFN-γ, and fail to proliferate. DN T cells from psoriasis patients are characterized by reduced DNA methylation of the IFNG gene and increased PD-1 expression. Furthermore, PD-1 positive DN T cells infiltrate the epidermis in psoriatic skin lesions. Our observations offer additional insight into the molecular pathophysiology of plaque psoriasis and show promise as potential disease biomarkers and/or therapeutic targets for future interventions. [ABSTRACT FROM AUTHOR]

• The present patient showed abnormally high expression of CaMK4 in effector memory T cells at the time of initial diagnosis. • After treatment, the expression of CaMK4 in effector memory T cells improved along with various organ damage and SLEDAI score. • High expression of CaMK4 in T cells of SLE patients may predict severe organ damage. [ABSTRACT FROM AUTHOR]

Kv1.3 channels regulate the activation/proliferation of effector memory T cells and thus play a critical role in the pathogenesis of autoimmune diseases. Using a combination of immunohistochemistry, confocal microscopy, flow cytometry and electrophysiology methods we observed a significant enrichment of activated Kv1.3 + memory T cells in psoriasis plaques and synovial fluid from patients with psoriasis/psoriatic arthritis (PsA) compared to non-lesional psoriatic skin, normal skin or peripheral blood lympho-mononuclear cells. In in vitro studies performed with lesional mononuclear cells or T cells derived from skin and joints of psoriatic disease, the small molecule Kv1.3 blocker PAP-1 dose-dependently inhibited proliferation and suppressed IL-2 and IFN-γ production. To further substantiate the pathologic role of Kv1.3 high T EM cells in psoriatic disease we tested whether PAP-1 is able to improve psoriatic disease pathology in the SCID mouse-psoriasis skin xenograft model. Following four weeks of daily treatment with 2% PAP-1 ointment we noticed about 50% reduction in the epidermal thickness (rete peg length) and the number of CD3 + lymphocytes/mm 2 of dermis decreased by 85%. Vehicle treated and untreated plaques in contrast remained unchanged and showed no reduction in epidermis thickness and infiltrating CD3 + T cells and HLA-DR + T cells. Based on these results we propose the development of Kv1.3 targeted topical immunotherapy for psoriasis and possibly for other inflammatory skin conditions, where effector memory T cells are involved in the pathogenesis. [ABSTRACT FROM AUTHOR]

Increased numbers of regulatory T (Treg) cells are found in synovial fluid from patients with rheumatoid arthritis (RASF) compared with peripheral blood. However, Treg cells in RASF have been shown to have a decreased capacity to suppress T cells. Here we phenotypically classified CD4+ T cells in RASF into six subsets based on the expression of CD45RA, CCR7, CD27 and CD28, and demonstrated that the CCR7−CD45RA−CD27+CD28+ TEM subset was significantly increased in synovial fluid compared with peripheral blood. In addition, the proportion of Foxp3+ Treg cells in the CCR7−CD45RA−CD27+CD28+ TEM subset was significantly increased in RASF. Furthermore, most of the Foxp3+ Treg cells in RASF were non-suppressive CD45RA−Foxp3low non-Treg cells, and the frequency of the non-Treg cells in the CCR7−CD45RA−CD27+CD28+ TEM subset was significantly increased in RASF. Our findings suggest that the pro-inflammatory environment in RA joints may induce the increase of CD45RA−Foxp3low non-Treg cells in synovial fluid. [ABSTRACT FROM AUTHOR]

Highlights: [•] We classified human CD4+ T cells into six novel subsets based on CD45RA, CCR7, CD27, and CD28. [•] The CD27+CD28+ TCM subset is significantly decreased in the CD4+ T cells from RA patients. [•] The proportion of TNF-α-producing cells in the CD27+CD28+ TEM subset was increased in RA. [•] The frequency of activated/effector Treg cells in the CD27+CD28+ TCM subset was decreased in RA. [•] The percentage of naïve Treg cells negatively correlated with RA disease activity. [ABSTRACT FROM AUTHOR]

Abstract: In utero priming to malaria antigens renders cord blood mononuclear cells (CBMC) more susceptible to productive HIV infection in vitro in the absence of exogenous stimulation. This provides a unique model to better understand mechanisms affecting lymphocyte susceptibility to HIV infection in vivo. Effector memory CD3+CD4+ T cells (TEM) were the exclusive initial targets of HIV with rapid spread to central memory cells. HIV susceptibility correlated with increased expression of CD25 and HLA-DR on TEM. Virus entered all samples equally, however gag/pol RNA was only detected in HIV susceptible samples, suggesting regulation of proviral gene transcription. Targeted analysis of human genes in memory T cells showed greater expression of IFNG, NFATc1, IRF1, FOS, and PPIA and decreased expression YY1 and TFCP2 in HIV susceptible samples. Thus fetal priming to exogenous antigens enhances specific proviral gene transcription pathways in effector memory cells that may increase risk of vertical transmission of HIV. [Copyright &y& Elsevier]

Abstract: Naïve and memory B- and T-cell subsets were examined with three-color flow cytometry in the peripheral blood of patients with rheumatoid arthritis (RA) in comparison with healthy controls, and their association with disease duration, activity and autoantibodies was investigated in order to reveal potential imprints of antigen-specific immune response in RA. The B-cell population consisted of significantly less naïve (58.1±3.9% versus 68.7±3.7%; p =0.04), and more IgD−/CD27+ memory B cells (19.6±2.1% versus 13.7±2.1%; p =0.04) compared to healthy subjects. In addition, strong correlation was demonstrated between disease duration and the percentage of memory B cells (p <0.0001). Increased CD8+ terminally differentiated effector memory/central memory T-cell ratio (1.35±0.35 versus 0.84±0.24) was also detected in RA patients compared with controls, which also correlated with the duration of RA (p =0.005). The frequency of memory B cells and CD8+ effector memory T cells correlated with the proportion of CD4+ effector memory lymphocytes, suggesting cooperation between immune cells. Our results reflect disturbances in B- and T-cell homeostasis characterized by the accumulation of memory B cells and a shift towards CD8+ terminally differentiated effector memory T cells in RA, suggesting ongoing, antigen-driven immune response and accelerated differentiation of B and T lymphocytes into effector cells. [Copyright &y& Elsevier]