Early interleukin 12 production by macrophages in response to mycobacterial infection depends on interferon gamma and tumor necrosis factor alpha.

Flesch, I; Hess, Jürgen; Huang, Sui; Aguet, Michel; Rothe, Joachim; Bluethmann, Horst; Kaufmann, S. H. E.

doi:10.1084/jem.181.5.1615

Cited by 320 publications

(180 citation statements)

References 39 publications

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“…[31][32][33][34][35][36] Besides being a key cytokine secreted by the T helper 1 (Th1) and T cytotoxic 1 (Tc1) cytotoxic clones supporting cytolytic immune responses, [37][38][39] it has also been suggested that IFN-␥ is able to initiate Th1 differentiation. 40 However, previously reported results in other tumor models have indicated variable effects, 11,41,42 which were mostly weaker than those of, for example, IL-2 or granulocytemacrophage colony-stimulating factor transfectants. 23,[43][44][45][46] The inhibition of tumor growth achieved by immunization with cells expressing IL-7 was similar to that obtained by IFN-␥-expressing cells, although somewhat weaker.…”

Section: Discussionmentioning

confidence: 51%

Regression of intracerebral rat glioma isografts by therapeutic subcutaneous immunization with interferon-γ, interleukin-7, or B7-1-transfected tumor cells

et al. 1999

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Progress in the definition of the roles of various costimulators and cytokines in determining the type and height of immune responses has made it important to explore genetically altered tumor cells expressing such molecules for therapeutic immunizations. We have studied the effect of therapeutic subcutaneous (s.c.) immunizations on the growth of preexisting intracerebral brain tumor isografts in the rat. Transfectant glioma cell clones expressing either rat interferon-␥ (IFN-␥), rat interleukin-7 (IL-7), or rat B7-1 were selected. After irradiation (80 Gy) the clones were used for immunization (administered in up to four s.c. doses in a hind leg over 14-day intervals starting 1 day after the intracranial isografting of the parental tumor). Significant growth inhibition of the intracerebral parental tumors was induced by transfectants expressing IFN-␥ and IL-7, respectively. The strongest effect was observed with IFN-␥-expressing cells, resulting in cures in 37% of the males and in 100% of the females. Immunization with IL-7 had a similar, strong initial effect, with significantly prolonged survival in the majority of the rats but a lower final cure rate (survival for Ͼ150 days). The B7-1-expressing tumor clones induced cures in seven of eight female rats; however, no cures were seen in the male rats. It was also shown that the B7-1-expressing cells were themselves strongly immunogenic in female rats, requiring high cell numbers to result in a progressively growing tumor upon s.c. isografting; this was not the case in male rats. As a whole, the results imply that despite the unfavorable location of intracerebral tumors, therapeutic s.c. immunizations with certain types of genetically altered tumor cells can induce complete regressions with permanent survival and without gross neurological or other apparent signs of brain damage. The present results demonstrate complete regressions when immunizations are initiated shortly after intracranial isografting, when the intracerebral tumor is small. therapeutic immunizations (i.e., initiating the immunization when the "challenge tumor" is already established), it is important to keep in mind that the induced immunity is intended to eliminate even higher cell numbers under conditions when tumors have already established their stromal organization and blood supply. For many tumors, the major obstacle for successful immunotherapy does not seem to be a lack of expression of target Ags or an absence of responding lymphocytes, but rather that the immune response is quantitatively and/or qualitatively insufficient to eliminate the required number of tumor cells. A well-recognized reason for weak tumor immunogenicity is that tumor cells frequently have a decreased expression of major histocompatibility complex (MHC) class I. 1,2 However, a much lower concentration of MHC class I seems to be required to make tumor cells sensitive to already activated, cytolytic effector cells.3 To achieve therapeutic efficiency, there is a great demand for various techniques to boost the generati...

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Section: Discussionmentioning

confidence: 51%

Regression of intracerebral rat glioma isografts by therapeutic subcutaneous immunization with interferon-γ, interleukin-7, or B7-1-transfected tumor cells

et al. 1999

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“…Although relatively uncommon in the population (3% to 4%), more than two thirds of ing interleukin-8, 33 interleukin-12, and interferon gamma. 34 The alternative explanation for the association between the alcoholic patients with the TNFA-A variant had steatohepatitis compared with just over a third of patients homozygous 0238 TNF-a polymorphism and ALD, is that it is in linkage disequilibrium with another functional gene or genes. The for the wild-type TNFA-G allele.…”

Section: Discussionmentioning

confidence: 99%

Association of a tumor necrosis factor promoter polymorphism with susceptibility to alcoholic steatohepatitis

et al. 1997

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bility to ALD have thus far focused primarily on genes encod-SEE EDITORIAL ON PAGE 232 ing ethanol metabolizing enzymes. 3 Results have been conflicting, but it would appear that the known polymorphisms of genes encoding the alcohol and aldehyde dehydroTwin concordance studies suggest that genetic factors play genase enymes and the ethanol-inducible cytochrome P450, a role in determining why only a minority of heavy drinkers CYP2E1, play only a minor role in the Caucasian populadevelop hepatitis and cirrhosis. Tumor necrosis factor a tion. [5][6][7] These results have led to a search for alternative ''can-(TNF-a) has emerged as the ''final common pathway'' in the didate genes'' potentially involved in determining individual pathogenesis of alcohol-related hepatic necro-inflammation.susceptibility to advanced ALD. We have examined the frequency of the two recently de-The cytokine tumor necrosis factor a (TNF-a) has recently scribed polymorphisms of the TNF-a promoter in 150 paemerged as an important mediator of hepatic necro-inflamtients with biopsy-proven alcoholic liver disease and 145 mation associated with excessive alcohol intake. 8 Investigahealthy volunteers. There was a significant excess of the rare tion of the role of TNF-a and other cytokines in alcoholic allele (TNFA-A; G 0238 r A) at position 0238 in patients with steatohepatitis was first stimulated by the striking similarity steatohepatitis compared with controls or patients without observed between the metabolic complications of ASH and this lesion. This is consistent with previous suggestions that the metabolic effects of cytokines, including TNF-a. 8 Inthe TNFA-A allele, which falls within a putative Y regulation creased TNF-a production by peripheral blood monocytes box of the TNF-a promoter, is associated with increased TNFand Kupffer cells has been shown in patients with ASH and a expression. No differences were observed for the polymoranimal models of alcoholic liver injury. 9,10 Several investigaphism at position 0308. (HEPATOLOGY 1997;26:143-146.)tors have shown increased plasma levels of TNF-a activity in patients with ASH 11-15 and some have shown a correlation In common with other end-organ complications of alcohol with liver function and mortality. 11,14 TNF-a is cytotoxic to abuse, severe liver disease develops in only a minority of sensitized hepatocytes and has been implicated as a proximal heavy drinkers. In several biopsy studies alcoholic steatohepmediator in experimental liver injury induced by Propionibacatitis (ASH), characterized by steatosis and necroinflammaterium acnes, galactosamine, lead and endotoxin, and ischtion, is present in 6% to 30% of heavy drinkers, with estabemia-reperfusion. 8 In humans, reversible hepatitis is one of lished cirrhosis in less than 20%. 1 Although some evidence the toxicities of human recombinant TNF-a administered for supports a dose-response relationship between alcohol contherapy to cancer patients. 16 sumption and risk of disease, 2 it is clear that factors other Recently, two polymorphi...

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“…It was reported that macrophages produce IL-12 upon stimulation by IFN-␥ and TNF-␣ (34,35), which, in turn, are produced by the BCG-induced ␥␦ ⌻ cells. IL-12 production, indirectly induced by ␥␦ T cells, may participate in the induction of CD8 T cells.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Lung γδ T Cells Following Intranasal Infection withMycobacterium bovisBacillus Calmette-Guérin

Dieli

Iványi

Marsh

et al. 2003

The Journal of Immunology

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The lungs are considered to have an impaired capacity to contain infection by pathogenic mycobacteria, even in the presence of effective systemic immunity. In an attempt to understand the underlying cellular mechanisms, we characterized the γδ T cell population following intranasal infection with Mycobacterium bovis bacillus Calmette-Guérin (BCG). The peak of γδ T cell expansion at 7 days postinfection preceded the 30 day peak of αβ T cell expansion and bacterial count. The expanded population of γδ T cells in the lungs of BCG-infected mice represents an expansion of the resident Vγ2 T cell subset as well as an influx of Vγ1 and of four different Vδ gene-bearing T cell subsets. The γδ T cells in the lungs of BCG-infected mice secreted IFN-γ following in vitro stimulation with ionomycin and PMA and were cytotoxic against BCG-infected peritoneal macrophages as well as against the uninfected J774 macrophage cell line. The cytotoxicity was selectively blocked by anti-γδ TCR mAb and strontium ions, suggesting a granule-exocytosis killing pathway. Depletion of γδ T cells by injection of specific mAb had no effect on the subsequent developing CD4 T cell response in the lungs of BCG-infected mice, but significantly reduced cytotoxic activity and IFN-γ production by lung CD8 T cells. Thus, γδ T cells in the lungs might help to control mycobacterial infection in the period between innate and classical adaptive immunity and may also play an important regulatory role in the subsequent onset of αβ T lymphocytes.

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Early interleukin 12 production by macrophages in response to mycobacterial infection depends on interferon gamma and tumor necrosis factor alpha.

Cited by 320 publications

References 39 publications

Regression of intracerebral rat glioma isografts by therapeutic subcutaneous immunization with interferon-γ, interleukin-7, or B7-1-transfected tumor cells

Regression of intracerebral rat glioma isografts by therapeutic subcutaneous immunization with interferon-γ, interleukin-7, or B7-1-transfected tumor cells

Association of a tumor necrosis factor promoter polymorphism with susceptibility to alcoholic steatohepatitis

Characterization of Lung γδ T Cells Following Intranasal Infection withMycobacterium bovisBacillus Calmette-Guérin

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