Interferon-gamma In CD4 Research Articles

Effects of novel probiotic strains of Bacillus pumilus and Bacillus subtilis on production, gut health, and immunity of broiler chickens raised under suboptimal conditions

Probiotics are being developed as alternatives to antibiotic growth promoters. The aim of the study was to investigate the effects of 2 novel strains of Bacillus pumilus and Bacillus subtilis on production, intestinal microbiota, gut health, and immunity of broilers raised under suboptimal conditions. Day-old chicks (Cobb 500, n = 2,073) were randomly assigned into 6 groups: Con group (group fed with basal diet), Ab group (group treated with virginiamycin), groups treated with 2 levels of B. pumilus (low dose: 3 × 108 cfu/kg of feed [BPL] and high dose: 1 × 109 cfu/kg [BPH]), and groups treated with 2 levels of B. subtilis (low dose: 3 × 108 cfu/kg [BSL] and high dose: 1 × 109 cfu/kg [BSH]). Production parameters were recorded weekly. Cecal tonsils and content as well as ileum samples were collected on day 14 and day 42. Cecal tonsils were used to sort T-regulatory cells (CD4+CD8–CD25+ and CD4+CD8+CD25+) to study expression of IL-10 and interferon gamma, whereas cecal content was used for bacterial culture. Ileum samples were used to measure gene expression of tight junction proteins, mucin, and cytokines. BW and feed intake increased in the Ab, BPL, BSL, and BSH groups compared with the Con group between day 35 and day 42. The CD4+CD8-CD25+ cells expressed high levels of IL-10 in the BSH group on day 14 and in the BPL, BSL, and BSH groups on day 42 and high levels of interferon gamma in the BPL, BSL, and BSH groups on day 14 and in the BSL and BSH groups on day 42. The expression of IL-10 and interferon gamma in CD4+CD8+CD25+ cells was higher only in the BSH group on day 14 and day 42. Cecal bacterial populations of genera, Lactobacillus (day 14 and day 42) and Clostridium (day 14), were higher in the BSH group. Expression of tight junction protein increased significantly in the ileum on day 14 in the BPL (occludin, zona occludens 1 [ZO-1]), BSL (occludin, ZO-1), and BSH (occludin, ZO-1, junctional adhesion molecule 2 [JAM-2]) groups compared with that in the Con group and declined in all groups except in the BSH group (occludin, ZO-1, JAM-2) on day 42. Expression of MUC2 and IL-17F increased in all groups on day 14 and remained high on day 42 in the BSL and BSH groups. Taken together, both Bacillus probiotics altered the intestinal and immune activities, particularly on day 14, suggesting beneficial influence of probiotics.

TIM-3 Genetic Variations Affect Susceptibility to Osteoarthritis by Interfering with Interferon Gamma in CD4+ T Cells.

Osteoarthritis (OA) is the most common type of arthritis, in which T cell responses and cytokines may play critical roles in the development of the disease. TIM-3 may affect immune responses and is correlated with decreased expression of interferon gamma (INF-γ) in CD4+ T cells. In the current study, we investigated the association between polymorphisms in the TIM-3 gene and susceptibility to OA. Two polymorphisms in TIM-3, -574G/T and +4259T/G polymorphisms, were identified in OA cases and healthy donors by polymerase chain reaction-restriction fragment length polymorphism method. Data revealed that the prevalence of TIM-3 +4259T/G genotype was significantly elevated in OA patients than in the healthy donors after adjustment (Odds ratio [OR] = 2.67, 95% confidence interval [CI] 1.32-5.11, P < 0.001). Similarly, the TIM-3 +4259G allele presented a positive association with the risk of OA after adjustment (OR = 2.58, 95% CI 1.29-4.82, P = 0.003). The TIM-3 -574G/T polymorphism did not show any correlation with the disease. We further examined whether the two TIM-3 polymorphisms could affect INF-γ expression in CD4+ T cells. Data revealed that subjects carrying polymorphic +4259TG genotype had significantly higher mRNA and protein levels of INF-γ in CD4+ T cells compared to wild-type GG genotype (P < 0.001 and P < 0.01). These results indicated that TIM-3 polymorphism is associated with increased susceptibility to OA possibly by upregulating INF-γ expression in CD4+ T cells.

Human T‐cell responses to oral streptococci in human PBMC‐NOD/SCID mice

We investigated cellular and humoral immune responses to oral biofilm bacteria, including Streptococcus mutans, Streptococcus anginosus, Streptococcus sobrinus, and Streptococcus sanguinis, in NOD/SCID mice immunized with human peripheral blood mononuclear cells (hu-PBMC-NOD/SCID mice) to explore the pathogenicity of each of those organisms in dental and oral inflammatory diseases. hu-PBMC-NOD/SCID mice were immunized by intraperitoneal injections with the whole cells of the streptococci once a week for 3 weeks. FACS analyses were used to determine the percentages of various hu-T cell types, as well as intracellular cytokine production of interleukin-4 and interferon-gamma. Serum IgG and IgM antibody levels in response to the streptococci were also determined by enzyme-linked immunosorbent assay. S. anginosus induced a significant amount of the proinflammatory cytokine interferon-gamma in CD4(+) and CD8(+) T cells in comparison with the other streptococci. However, there was no significant differences between the streptococci in interleukin-4 production by CD4(+) and CD8(+) T cells after inoculation. Further, S. mutans significantly induced human anti-S. mutans IgG, IgG(1), IgG(2), and IgM antibodies in comparison with the other organisms. In conclusion, S. anginosus up-regulated Th1 and Tc1 cells, and S. mutans led to increasing levels of their antibodies, which was associated with the induction of Th2 cells. These results may contribute to a better understanding of human lymphocyte interactions to biofilm bacteria, along with their impact on dental and mucosal inflammatory diseases, as well as endocarditis.

Inhibitory effects of voluntary wheel exercise on apoptosis in splenic lymphocyte subsets of C57BL/6 mice.

Two-month-old mice were placed in cages with (Ex) or without exercise running wheels with free access to the wheel 24 h/day for 10 mo. An equal amount of food for both groups was provided daily. Ex mice ran an average of 33.67 km/wk initially, and exercise decreased gradually with age. Ex mice had gained an average of 43.5% less body weight at the end of the experiment. Although serum lipid peroxides were not altered by exercise, superoxide dismutase and glutathione peroxidase activities in serum were significantly increased. Flow cytometric analysis of spleen cells revealed an increased percentage of CD8+ T cells and a decreased percentage of CD19+ B cells in Ex mice (P < 0.05). Exercise decreased apoptosis in total splenocytes and CD4+ cells incubated with medium alone or with H(2)O(2), dexamethasone, tumor necrosis factor-alpha (TNF-alpha), or anti-CD3 monoclonal antibody (P < 0.05) and CD8+ cells with medium alone or with TNF-alpha (P < 0.05). Even though exercise did not alter the intracellular cytokines (TNF-alpha and interleukin-2) or Fas ligand, it did significantly lower interferon-gamma in CD4+ and CD8+ cells (P < 0.05). In summary, voluntary wheel exercise appears to decrease H(2)O(2)-induced apoptosis in immune cells as well as decrease interferon-gamma production.

Divergent roles of interferon-gamma in CD4 t cell-mediated graft-versus-host disease (Gvhd) Contigent on the conditioning of the recipient

Cytokines have been demonstrated to play a pivotal role in graft-versus-host disease (GVHD), at times being both protective and deleterious. Interferon gamma (IFNγ) as been shown to play a protective role in acute GVHD following lethal total body irradiation (TBI) and bone marrow transplant in full MHC mismatched murine models of the disease. In this report, we show that CD4+ T cells from interferon-gamma knockout (KO) mice accelerate GVHD in a single MHC II mismatched murine model (C57BL/6 into bm12) following lethal TBI and bone marrow transplant. In marked contrast, use of these same CD4+ T cells results in protection from GVHD associated anemia and bone marrow aplasia following infusion into sublethally irradiated mice using the same strain combination. Bone marrow cellularities and hematopoietic progenitor cell content were markedly decreased in recipients of wild type CD4+ enriched lymph node cells following sublethal irradiation. Bone marrow cellularities and CFU-GM in recipients of IFNγ-deficient CD4+ T cells were not significantly different from mice that received only sublethal irradiation. These results demonstrate the requirement of interferon-gamma for CD4+ T cell-mediated destruction of allogeneic hematopoietic cells which is primary manifested in sublethal conditioning whereas in lethal conditioning tissue damage affecting solid organs (skin, gut, liver) occurs and interferon is protective.