Suppression of Cytokine Production in T Helper Type 2 Cells by Nitric Oxide in Comparison with T Helper Type 1 Cells

Nukaya, Ikuei; Takagi, Katsuyuki; Kawabe, Takefumi; Suketa, Yasunobu

doi:10.1111/j.1348-0421.1995.tb03246.x

Cited by 17 publications

(16 citation statements)

References 18 publications

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“…After Bonferroni's adjustment, the distribution analysis revealed that the (CCTTT) 14 allele was significantly over-represented in the control group (13.5% versus 6.2%, p = 0.044; OR = 0.39; 95% CI = 0.207-0.735, corrected for age and sex). Considering the presence/absence of at least one (CCTTT) 14 allele in the two studied populations, we found that 11.5% of the RRMS patients and 25.3% of the healthy subjects carried this NOS2A allele, with a statistically significant difference (χ 2 =8.843, p = 0.003). This data seems to confer a significant protection against MS (OR = 0.348; 95% CI = 0.174-0.693, corrected for age and gender).…”

Section: Resultsmentioning

confidence: 97%

“…This test was also applied to compare age at examination, age at disease onset, disease duration and brain volumes (GM, WM) between MS patients carrying and not carrying the (CCTTT) 14 allele. MannWhitney U-test was used to compare EDSS values.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies indicated that NO is not only a potent cytotoxic and antimicrobial agent but it also exhibits significant immunoregulatory activity by balancing the type-1 and type-2 T-helper lymphocytes reaction [14,15]. Particularly the iNOS is believed to play a key role during the host defense and the inflammation processes of demyelinating diseases like MS [13].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Preliminary evidences of a NOS2A protective effect from Relapsing–Remitting Multiple Sclerosis

Manna

Liguori

Valentino

et al. 2008

Journal of the Neurological Sciences

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Section: Resultsmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Preliminary evidences of a NOS2A protective effect from Relapsing–Remitting Multiple Sclerosis

Manna

Liguori

Valentino

et al. 2008

Journal of the Neurological Sciences

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“…Thus, reduced IFN-␥ levels may be due to a combination of poor CD8-cell proliferation and thus fewer IFN-␥-producing cells in the cultures, combined with an absence of help from IL-4. Moreover, there have been multiple reports demonstrating that NO is capable of inhibiting cytokine production by T cells (6,36,42,44,47). The role of NO in downregulating type 1 responses is underscored by research utilizing iNOS Ϫ/Ϫ mice, which develop enhanced type 1 cellular and humoral responses following vaccination with attenuated S. mansoni cercariae (22).…”

Section: Vol 70 2002 Il-4 Regulates No-mediated T-cell Function Inhmentioning

confidence: 99%

Central Role for Interleukin-4 in Regulating Nitric Oxide-Mediated Inhibition of T-Cell Proliferation and Gamma Interferon Production in Schistosomiasis

et al. 2002

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Interleukin-4 (IL-4) plays an important role in several areas of T-cell biology, including the development of Th2 responses (25) and blocking Th1 effector mechanisms mediated by gamma interferon (IFN-␥), such as inducible nitric oxide synthase (iNOS) induction (1,10,28,43,50). Further, IL-4 can inhibit NO production by upregulating arginase expression, thereby providing an alternative pathway for metabolism of L-arginine, the precursor for NO (34).The outcome of schistosome infection in IL-4 Ϫ/Ϫ animals is different from that in wild-type (WT) mice (13,14,18). WT mice normally develop a strong Th2 response and survive infection (14,18). Survival is attributed to the ability of Th2 cells to orchestrate granulomatous lesions which sequester parasite eggs away from surrounding liver tissue while at the same time secreting cytokines that are selectively anti-inflammatory (4,13,15,18,24). Infected IL-4 Ϫ/Ϫ mice, in contrast, fail to develop a Th2 response and produce elevated levels of inflammatory mediators, such as IFN-␥ and NO, and develop severe cachexia and die despite still being able to make adequate granulomas (13,14,18).An interesting feature of schistosomiasis in infected IL-4mice is the failure of these animals to develop the splenomegaly that is characteristic of infection in WT mice (39). Since NO is known to inhibit T-cell proliferation (2,3,8,37,48,50), we hypothesized that increased NO levels in IL-4 Ϫ/Ϫ animals could be contributing to the lack of splenomegaly by inhibiting the proliferation of lymphocytes during infection. Our findings presented here support this view. MATERIALS AND METHODSParasites and mice. IL-4 Ϫ/Ϫ C57BL/6 (B6) mice (14) were bred at Cornell University. WT B6 mice were obtained from Taconic Farms, Germantown, N.Y. Mice were anesthetized with sodium pentobarbitone intraperitoneally (i.p.), and each was infected percutaneously with approximately 70 Schistosoma mansoni cercariae (NMRI strain). Mice were weighed using a spring balance (Forestry Suppliers, Jackson, Miss.). Experiments were terminated once infected IL-4 Ϫ/Ϫ mice lost ϳ20% of their body weight (14); mice were euthanatized with CO 2 .Cell cultures. Spleens were harvested, and single-cell suspensions of pooled samples were prepared using sterile 70-m-pore-size nylon mesh (Becton Dickinson, Franklin Lakes, N.J.) and Dulbecco minimal essential medium (DMEM). Erythrocytes were lysed using ammonium chloride. Viable cells were counted using trypan blue exclusion and resuspended at 10 7 /ml in DMEM containing 30 mM HEPES, 100 U of penicillin/ml, 100 g of streptomycin/ml, 2 mM glutamine, 5 ϫ 10 Ϫ5 M 2-mercaptoethanol, and 10% hiFCS (complete medium). Cells were incubated alone or were stimulated with 50 g of soluble egg antigen (SEA)/ml (11) or with plate-bound anti-CD3 monoclonal antibody (MAb) (Pharmingen, San Diego, Calif.), 0.5 g/well, with or without aminoguanidine (AMG) (hemisulfate salt, 1 mM), in 96-well flat-bottom plates in 5% CO 2 at 37°C. Cell culture supernatants were collected at 72 h and stored at Ϫ20°C until cyto...

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“…Although suppression of IL-4 production by Th2 clones has been observed (Nukaya et al, 1995), it appears more likely that NO exerts either neutral (Marcinkiewicz et al, 1996) or positive (Chang et al, 1997) effects in the overall development of Th2-type immunity. Suppression of by NO may lead to enhanced IL-4 production through Th1/Th2 cross-regulation.…”

Section: T-cell Activation and Cytokine Synthesismentioning

confidence: 96%

Immunomodulatory Actions of Nitric Oxide

McInnes

Liew

2002

Nitric Oxide and Infection

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Suppression of Cytokine Production in T Helper Type 2 Cells by Nitric Oxide in Comparison with T Helper Type 1 Cells

Cited by 17 publications

References 18 publications

Preliminary evidences of a NOS2A protective effect from Relapsing–Remitting Multiple Sclerosis

Preliminary evidences of a NOS2A protective effect from Relapsing–Remitting Multiple Sclerosis

Central Role for Interleukin-4 in Regulating Nitric Oxide-Mediated Inhibition of T-Cell Proliferation and Gamma Interferon Production in Schistosomiasis

Immunomodulatory Actions of Nitric Oxide

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