IL-4 induces allergic-like inflammatory disease and alters T cell development in transgenic mice

Tepper, Robert I.; Levinson, Douglas A.; Stanger, Ben Z.; Campos-Torres, Juanita; Abbas, Abul K.; Leder, Philip

doi:10.1016/0092-8674(90)90011-3

Cited by 390 publications

(190 citation statements)

References 41 publications

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“…largely due to a decrease in CD4^ cells as was also seen in some IL-4 transgenic mice [42]. The IgE and IgG] hyperproduction that we observed in our IL-4 treated mice was also seen in some IL-4 transgenics [42,43]. In all described IL-4 transgenic mice the MHC class II expression on B cells increased [43.44].…”

Section: Discussionmentioning

confidence: 62%

Prolonged In Vivo IL‐4 Treatment Inhibits Antigen‐Specific IgG1 and IgE Formation

1994

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van Ommen R. Vredendaal AECM, Savelkoul HFJ. Prolonged In Vivo IL-4 Treatment Inhibits Antigen-Specific IgGi and IgE Formation. Scand J Immunol I994;40:l-9 IL-4 is obligatory for primary IgE responses, whereas primary IgGi and secondary IgE responses are partially IL-4 independent. To investigate the effect of IL-4 on the antigen-specific memory formation for these isotypes, BALB/c mice were treated after primary TNP-K.LH immunization with recombinant IL-4 for a period of 4 months. This prolonged presence of a high IL-4 level resulted in increased serum levels of total IgG, and IgE, whereas total IgG2^ did not change. The expression of CD23, but not I-A*", increased on the splenic B cells. IL-4 treatment did not affect the IL-4 production by Con A stimulated spleen cells, whereas it did decrease the IFN-7 production. In the same mice the TNP-specific IgGi and IgE serum levels, however, were decreased. Similar results were found when the antigen was continuously present during the IL-4 treatment. Furthermore, it was shown that IL-4 decreased the formation of IgGj and IgE memory cells. These results point to different effects of IL-4 in regulating antigen-specific and bystander responses.R. van Ommen.

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Section: Discussionmentioning

confidence: 62%

Prolonged In Vivo IL‐4 Treatment Inhibits Antigen‐Specific IgG1 and IgE Formation

1994

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“…In this respect, it should be noted that overexpression of IL-4 was lethal in IL-4 transgenic mice and a phase I study of recombinant human IL-4 resulted in liver dysfunction, indicating direct hepatotoxicity of IL-4. 37,38 Conventional microscopic examination 5 days after allograft and gene transfer showed a comparable leukocyte infiltration between untreated hearts and those treated with 10 9 p.f.u. of Addl324, AdIL-4 or AdIL-10.…”

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confidence: 87%

Interleukin-10 produced by recombinant adenovirus prolongs survival of cardiac allografts in rats

et al. 2000

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“…While preparing this manuscript we became aware ofdata by Tepper et al (68) showing that an IL4 transgene under the control ofthe u H chain enhancer results in the increased expression of 11,4 by -T-as well as B-lineage cells . These mice demonstrate most of the phenotypic alterations in Vintage cells we have observed in lck-IL4 mice, confirming that these results are attributable to the IL4 gene product itself.…”

Section: Reversal Of Thymic Abnormalities In Lck-il4 Mice Treated Withmentioning

confidence: 99%

Interleukin 4 expressed in situ selectively alters thymocyte development.

Lewis

Forbush

et al. 1991

The Journal of Experimental Medicine

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SummaryUsing a transgenic mouse model we show that increased intrathymic expression of interleukin 4 (IL4) significantly perturbs the development of thymocytes. Transgenic double-positive (CD4+CD8+) thymocytes, which are present in dramatically reduced numbers, exhibit increased T cell receptor (TCR) expression and increased mobilization ofcalcium mediated by these receptors. In contrast, transgenic single-positive (CD4+CD8 -and CD4 -CD8+) thymocytes and peripheral T cells exhibit decreased TCRmediated calcium mobilization. The development of CD4 -CD8+ thymocytes is significantly perturbed by 114 expressed in vivo; only peripheral CD4+ T cells are found in significant numbers in transgenic mice, while CD4 -CD8+ thymocytes are present in increased numbers, apparently because of their failure to emigrate to the periphery. In contrast to these selective effects on T cell development, no significant differences in the numbers ofB cells or mast cells, or in the plasma levels of IgE and IgG1 are observed between transgenic and control mice. These observations suggest that 114 in vivo exerts its major effects locally rather than systemically, even when its expression is constitutively increased.

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IL-4 induces allergic-like inflammatory disease and alters T cell development in transgenic mice

Cited by 390 publications

References 41 publications

Prolonged In Vivo IL‐4 Treatment Inhibits Antigen‐Specific IgG1 and IgE Formation

Prolonged In Vivo IL‐4 Treatment Inhibits Antigen‐Specific IgG1 and IgE Formation

Interleukin-10 produced by recombinant adenovirus prolongs survival of cardiac allografts in rats

Interleukin 4 expressed in situ selectively alters thymocyte development.

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