Bovine interleukin-12 and modulation of IFNγ production

Collins, Robert A.; Howard, Christopher; Duggan, Sara E.; Werling, Dirk

doi:10.1016/s0165-2427(99)00020-3

Cited by 57 publications

(31 citation statements)

References 38 publications

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“…However, Plain et al obtained an increase in IFN-␥ production for only 2 days (20). Our results corroborate findings from previous studies that investigated the feasibility of using recombinant IL-12 to stabilize CMI response in vitro (18,19). In addition, our data extend current knowledge about the potential use of IL-7 as a synergistic cytokine that is crucial to T lymphocyte survival to maintain cell size, promote glucose and protein metabolism, and inhibit apoptotic processes.…”

Section: Figsupporting

confidence: 90%

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Stimulation of Bovine Whole-Blood Samples Cultured in Media Supplemented with Recombinant Interleukin-7 (IL-7) and IL-12 Extends the Life Span of the Gamma Interferon Assay To Detect Mycobacterium bovis-Infected Cattle

et al. 2016

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The gamma interferon (IFN-␥) assay is widely used to measure cell-mediated immune (CMI) response for the early detection of tuberculosis infection. Processing whole-blood samples for CMI-based diagnostics is time sensitive and usually must occur within 8 h of collection to ensure optimal assay performance. In this study, we developed and tested a modified protocol, in which whole-blood samples from Mycobacterium bovis-infected cattle were diluted 1:1 in RPMI medium containing 0.3% fetal bovine serum (FBS) added or not to recombinant mouse interleukin-7 (rmIL-7) or rmIL-12, alone or in combination, and stored at 4°C. At 3 and 6 days postcollection, the diluted blood samples were adjusted to 10% FBS, dispensed into culture trays, stimulated with a bovine purified protein derivative from M. bovis, and incubated at 37°C in 5% CO 2 in air. Plasma was removed and assayed for an IFN-␥ response using bovine IFN-␥ enzyme-linked immunosorbent assay (ELISA) (Bovigam). The results were then compared with those obtained from the conventional procedure. The IFN-␥ responses of the samples stored up to 6 days postcollection in the supplemented RPMI medium were similar to those observed in the samples processed within 8 h after sampling, indicating that lymphocyte vitality and response were preserved. The addition of rmIL-7 and rmIL-12, alone or in combination, to culture medium can enhance lymphocyte survival and thus extends the time limit within which the IFN-␥ assay can be applied as a diagnostic tool in bovine tuberculosis surveillance and eradication. Bovine tuberculosis (bTB) is a chronic debilitating disease that can take years before causing clinical signs to develop. bTB eradication programs in cattle are based on the application of diagnostic tests and the culling of reactor cattle (1). The standard test for the antemortem screening of infected animals is the tuberculin skin test, which is widely used in veterinary and human medicine. Several factors can influence the specificity and sensitivity of the tuberculin intradermal test (IDT). One of its main disadvantages is that cattle may sometimes be infected by other Mycobacterium strains that produce cross-reactivity that can be easily mistaken for a positive Mycobacterium bovis infection response. In addition, it has been observed that animal age and housing can also affect test specificity (2) and that the test can turn negative in the presence of a tuberculosis infection in immunosuppressed animals. To overcome these limitations, a cell-mediated immunity (CMI) response can be determined in vitro by measuring the gamma interferon (IFN-␥) produced by memory T lymphocytes from M. bovis-infected animals. IFN-␥ in the plasma of blood cultures is measured by enzyme-linked immunosorbent assay (ELISA). The IFN-␥ assay has been shown to be a sensitive and specific test to detect tuberculosis in cattle (3) and other animal species, including sheep (4), goats (5), buffalo (6), cervids (7), and pigs (8), and it is effective for identifying infected animals at early stages of in...

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Section: Figsupporting

confidence: 90%

“…The roles of these two cytokines in prolonging cell survival and enhancing IFN-␥ production (IL-12) have been investigated by others (18)(19)(20). However, Plain et al obtained an increase in IFN-␥ production for only 2 days (20).…”

Section: Figmentioning

confidence: 99%

Stimulation of Bovine Whole-Blood Samples Cultured in Media Supplemented with Recombinant Interleukin-7 (IL-7) and IL-12 Extends the Life Span of the Gamma Interferon Assay To Detect Mycobacterium bovis-Infected Cattle

et al. 2016

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“…The recent development of real-time fluorogenic PCR technology permits rapid, high-throughput analysis of gene expression. Real-time PCR assays have been described for a panel of bovine (8,34), equine (35), human (24,53), and murine (24) cytokines. To date, there have been few reports of studies in which real-time PCR was used to analyze the expression of cytokines in pigs (1,11,36,52).…”

mentioning

confidence: 99%

Localized Multigene Expression Patterns Support an Evolving Th1/Th2-Like Paradigm in Response to Infections withToxoplasma gondiiandAscaris suum

et al. 2005

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Section: Discussionmentioning

confidence: 99%

“…That both antigen presentation and high levels of IL-12 are involved in increased IFN-γ production is suggested from studies by Collins, et al (1999), which showed that antigen substantially enhances the IFN-γ response by sensitized bovine PBMC to IL-12 stimulation (Collins et al, 1999). Whereas unstimulated PBMC cultured in the presence of IL-12 for 48 hours produced only small amounts of IFN-γ (5-10 ng/mL), IFN-γ concentrations of 25-100 ng/mL were observed when PBMC from sensitized animals were cultured in the presence of antigen plus IL-12 (Collins et al, 1999). Other have shown that IL-12 mRNA expression is increased in M. paratuberculosis-infected macrophages in vitro within 6 hours of infection; this expression remains high through 24 hours but decreases to control levels by 72 hours after infection (Weiss et al, 2002), suggesting that M. paratuberculosis-infected macrophages rapidly produce IL-12 to enhance the developing T cell response.…”

Section: Discussionmentioning

confidence: 99%

Failure of antigen-stimulated γδ T cells and CD4+ T cells from sensitized cattle to upregulate nitric oxide and mycobactericidal activity of autologous Mycobacterium avium subsp. paratuberculosis-infected macrophages

Simutis

Jones

Hostetter

2007

Veterinary Immunology and Immunopathology

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The function of γδ T cells during ruminant paratuberculosis (Johne's disease) is presently unknown. An ex vivo system was used to test the hypothesis that γδ T cells are capable of activating Mycobacterium avium subsp. paratuberculosis-(M. paratuberculosis)-infected macrophages. Peripheral blood-derived macrophages were infected in vitro with live M. paratuberculosis, and autologous LN-derived γδ T cells or CD4+ T cells were co-cultured with infected macrophages for 48 hours, at which time bacterial survival as well as production of nitrites and IFN-γ were evaluated. Incubation of M. paratuberculosis-infected macrophages with autologous γδ T cells did not result in reduced intracellular bacterial viability compared to infected macrophage cultures without added T cells. IFN-γ production by-infected cultures containing added γδ T cells was not enhanced compared to that of infected macrophages alone. Although infection of macrophage cultures caused increased production of nitrites at both post-infection day (PID) 0 and PID 60, the addition of γδ T cells did not further increase nitrite production. In contrast, addition of PPD-stimulated CD4+ T cells obtained at PID 60 to M. paratuberculosis-infected macrophages resulted in significantly increased IFN-γ production compared to cultures without added T cells or cultures containing unstimulated CD4+ T cells or unstimulated or antigen-stimulated γδ T cells. However, the increased production of IFN-γ by co-cultures containing PPD-stimulated CD4+ T cells did not result in increased bacterial killing or increased production of nitrites compared to cultures without added T cells. In additional in vitro experiments, M. paratuberculosis-infected macrophages, but not uninfected macrophages, were unable to increase nitrite production when stimulated with recombinant IFN-γ. Taken together, the data suggest that (1) γδ T cells do not produce significant IFN-γ and do not significantly increase NO production from M. paratuberculosis-infected macrophages in vitro, (2) the production of significant IFN-γ by antigen-stimulated CD4+ T cells from infected calves is insufficient to enhance mycobacterial killing or nitrite production by infected macrophages, and (3) macrophages may have an impaired NO response following intracellular M. paratuberculosis infection, even in the presence of significant concentrations of IFN-γ.

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Bovine interleukin-12 and modulation of IFNγ production

Cited by 57 publications

References 38 publications

Stimulation of Bovine Whole-Blood Samples Cultured in Media Supplemented with Recombinant Interleukin-7 (IL-7) and IL-12 Extends the Life Span of the Gamma Interferon Assay To Detect Mycobacterium bovis-Infected Cattle

Stimulation of Bovine Whole-Blood Samples Cultured in Media Supplemented with Recombinant Interleukin-7 (IL-7) and IL-12 Extends the Life Span of the Gamma Interferon Assay To Detect Mycobacterium bovis-Infected Cattle

Localized Multigene Expression Patterns Support an Evolving Th1/Th2-Like Paradigm in Response to Infections withToxoplasma gondiiandAscaris suum

Failure of antigen-stimulated γδ T cells and CD4+ T cells from sensitized cattle to upregulate nitric oxide and mycobactericidal activity of autologous Mycobacterium avium subsp. paratuberculosis-infected macrophages

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