THE PRODUCTION OF SOLUBLE INTERLEUKIN 4 RECEPTORS IS PREFERENTIALLY REGULATED BY THE MURINE Th2CELL SUBSET

Fernández-Botrán, Rafael; Chilton, Paula M.; Ma, Yuhe; Windsor, Jana; Street, Nancy E.

doi:10.1006/cyto.1996.0151

Cited by 12 publications

(11 citation statements)

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“…Moreover, it could also be an indirect consequence of the relative lack of inhibitory mechanisms on sIL-4R expression promoted by Th1 cells. Evidence from previous studies comparing clones of murine CD4 ϩ T cell subsets have indeed suggested that only Th2 clones significantly up-regulate expression of sIL-4R following antigenic stimulation, thus giving support to the idea that activated CD4 ϩ Th2 cells might be directly responsible for a good portion of secreted sIL-4R [26]. The existence of Th1 subset-derived inhibitory factors on sIL-4R production appears very unlikely because neither Th1-derived supernatants nor rIFN-␥ demonstrated any inhibitory effect on sIL-4R production by Th2 cell lines or normal splenic cells.…”

Section: Discussionmentioning

confidence: 69%

“…Supernatants were collected and stored frozen until assay. Th1-supernatants were obtained by culturing the CD4 ϩ T cell clones, HDK-1 and D1.1, for 48 h in the presence of their specific antigen and irradiated syngeneic splenic cells, as described [26].…”

Section: Pln and Spleen Cell Preparations And Culturementioning

confidence: 99%

“…The levels of IL-4, IFN-␥, and sIL-4R in culture supernatants were assayed by two-site ELISAs, as described [26]. In the assays for sIL-4R, the aliquots of the supernatants were pre-incubated with 11B11 (anti-IL-4 mAb, 10 µg/mL) in order to prevent interference from endogenous IL-4 [24].…”

Section: Cytokine Assaysmentioning

confidence: 99%

“…For example, both serum sIL-4R levels and sIL-4R production in vitro were found to parallel the development of Th2 responses in mice infected with the parasitic trematode Schistosoma mansoni [25]. Moreover, analysis of established murine Th1 and Th2 CD4 ϩ T cell lines showed that, although both types of cells produced low basal levels of sIL-4R, only the Th2 cell lines up-regulated expression of sIL-4R on antigenic stimulation [26]. However, the production of sIL-4R during Th1 responses in vivo and the potential effects of Th1-associated cytokines in the production of sIL-4R remained unknown.…”

Section: Introductionmentioning

confidence: 98%

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Regulation of the production of soluble IL-4 receptors in murine cutaneous leishmaniasis. The roles of IL-12 and IL-4

Fernández-Botrán

Chilton

Hondowicz

et al. 1999

Journal of Leukocyte Biology

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These studies were undertaken with the purpose of elucidating the key signals involved in the regulation of the production of soluble interleukin-4 receptors (sIL-4R) in mice during Th1 and Th2 responses to infection with the parasite Leishmania major. Our results showed that the production of sIL-4R was consistently higher in lymph node cell cultures from animals mounting a predominant Th2 response (BALB/c mice), and that sIL-4R production paralleled that of IL-4 in both mouse strains, even in the presence of a dominant Th1 response (C3H/FeJ mice). Consistently, administration of anti-IL-12 antibodies to infected C3H/ FeJ mice induced a switch from a Th1-to a Th2-type response and resulted in enhanced production of sIL-4R. Addition of rIL-12 to splenic cell cultures, however, was found not to have a direct effect on sIL-4R production induced by IL-4 or T cell mitogens. Moreover, the production of sIL-4R appears to be little influenced by Th1-produced cytokines, inasmuch as recombinant interferon-␥ or supernatants derived from antigenstimulated Th1 clones did not affect the production of sIL-4R by activated splenic cultures. Despite its correlation with Th2 responses, the presence of IL-4 was not an absolute requirement for the up-regulation of the expression of sIL-4R because increased levels could be induced on cells obtained from IL-4 -/-mice. These results indicate that, although enhanced sIL-4R production is a feature related to the activation and/or generation of Th2 responses, it is not absolutely dependent on IL-4 or directly inhibited by IL-12 or Th1 cytokines. J. Leukoc. Biol. 66: 481-488; 1999.

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Section: Discussionmentioning

confidence: 69%

Section: Pln and Spleen Cell Preparations And Culturementioning

confidence: 99%

Section: Cytokine Assaysmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Regulation of the production of soluble IL-4 receptors in murine cutaneous leishmaniasis. The roles of IL-12 and IL-4

Fernández-Botrán

Chilton

Hondowicz

et al. 1999

Journal of Leukocyte Biology

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“…While in mice sIL–4R production was found to be enhanced in Th2 cells [26, 27]and upregulated during an ongoing Th2 immune response in vivo [10, 17], in man so far there is no evidence that sIL–4R production is an active component of a cellular immune response and possibly regulated by cytokines involved in T cell differentiation. Here, IL–4 was found to enhance sIL–4R production by activated CD45RA+, but less by CD45R0+ T cells reflecting enhanced IL–4 susceptibility of CD45RA+ T cells [24].…”

Section: Discussionmentioning

confidence: 99%

Soluble Human Interleukin–4 Receptor Is Produced by Activated T Cells under the Control of Metalloproteinases

Jung¹,

Schrader²,

Hellwig³

et al. 1999

Int Arch Allergy Immunol

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Background: Soluble interleukin 4 receptors (sIL–4R) are present in biological fluids. In contrast to mice, in man no distinct mRNA coding for sIL–4R has been described, suggesting that human sIL–4R is exclusively produced by proteolytic cleavage of the cell surface receptor. It is not known whether human sIL–4R is actively produced during an immune response. Methods: Human purified T cells, CD4+, CD8+, CD45RA+ and CD45R0+ T cell subpopulations were activated in vitro. sIL–4R was determined in the supernatants, cell surface IL–4R was measured by flow cytometry and RT–PCR. Results: Recombinant sIL–4R inhibited IL–4–mediated proliferation and IL–5 upregulation by T cells. sIL–4R could be detected at low levels in supernatants of nonactivated T cells, but at high levels following TCR engagement. This response was paralleled by enhanced transcription and de novo synthesis of the human cell surface IL–4R. Both, activated naive CD45RA+ and memory CD45R0+ T cells, produced sIL–4R with long–lasting kinetics. IL–4 increased sIL–4R production by activated CD45RA+, but there was less of an increase by CD45R0+ T cells. In addition, interferon–γ enhanced sIL–4R production. Cycloheximide and dexamethasone inhibited sIL–4R production by activated T cells, but did not abolish constitutive release of sIL–4R. Phosphoramidon and 1,10–phenanthroline dose–dependently inhibited shedding of the IL–4R, even in nonactivated T cells. Conclusion: The production of human sIL–4R by T cells is regulated by TCR stimuli, IL–4 and IFN–γ and needs the activity of metalloproteinases. Thus, sIL–4R should be regarded as inducible and due to its IL–4–antagonizing activity an immunoregulatory molecule.

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Regulation of the Expression of the Soluble and Membrane Forms of the Murine IL-4 Receptor

Chilton

Fernández-Botrán

1997

Cellular Immunology

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THE PRODUCTION OF SOLUBLE INTERLEUKIN 4 RECEPTORS IS PREFERENTIALLY REGULATED BY THE MURINE Th2CELL SUBSET

Cited by 12 publications

References 0 publications

Regulation of the production of soluble IL-4 receptors in murine cutaneous leishmaniasis. The roles of IL-12 and IL-4

Regulation of the production of soluble IL-4 receptors in murine cutaneous leishmaniasis. The roles of IL-12 and IL-4

Soluble Human Interleukin–4 Receptor Is Produced by Activated T Cells under the Control of Metalloproteinases

Regulation of the Expression of the Soluble and Membrane Forms of the Murine IL-4 Receptor

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