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Adoptive transfer of low numbers of CD4+ T cells into SCID mice chronically treated with soluble IL-4 receptor does not prevent engraftment of IL-4-producing T cells.

Abstract：

:After intravenous injection of 10(5) purified, lymph node (LN)-derived dm2 (H-2d/Ld-) CD4+ T cells into young C.B-17 scid/scid (severe combined immunodeficiency, SCID) mice (H-2d/Ld+), the transplanted Ld-T cells show a selective pattern of engraftment: they repopulate the spleen, the lamina propria of the small intestine and the mesenteric LN (but not other peripheral LN) of the immunodeficient host. CD4+ cells repopulating different lymphoid organs of the SCID recipient mice produce interleukin-2 (IL-2) and interleukin-4 (IL-4) in response to polyclonal stimulation in vitro. Some evidence has recently been provided that cytokines (e.g. IL-4) present at the site of antigen stimulation in vivo decisively influence the pattern of cytokines expressed by T cells activated at these sites. We therefore asked if neutralization of IL-4 by chronic treatment of SCID mice with high doses of recombinant soluble IL-4 receptor (sIL-4R) changes the IL-4 or IL-2 expression pattern of CD4+ T cells adoptively transferred into young SCID recipients. Transplanted SCID mice were chronically treated with two different, recombinant murine sIL-4R proteins. The experimental series further included groups of transplanted SCID mice treated with a recombinant human sIL-4R protein (which does not bind murine IL-4), treated with the anti-murine IL-4 monoclonal antibody (MoAb) 11B11, or non-treated. Transplanted SCID mice treated with the recombinant murine sIL-4R protein preparations displayed detectable sIL-4R serum levels, which demonstrates that the substitution therapy could maintain neutralizing serum levels of anti-IL-4 activity in SCID mice. By contrast, no serum sIL-4R levels were detectable in the sensitive ELISA readout in transplanted SCID mice which were non-treated, treated with the MoAb 11B11, or treated with the recombinant humans sIL-4R protein. The efficiency and the pattern of CD4+ T-cell engraftment, and the lymphokine-producing phenotype of the engrafted dm2 CD4+ cells, was not affected by the continuous IL-4-neutralizing treatment of mice with either the MoAb 11B11 or the soluble IL-4R preparations. Hence, in contrast to the published evidence of the dramatic effect of IL-4 on the lymphokine-producing phenotype of CD4+ T cells stimulated in vitro or in vivo, the chronic suppression in vivo of IL-4 activity (by either different sIL4-R protein constructs, or by the anti-IL-4 MoAb 11B11) did not lead to preferential engraftment of Th1-type CD4+ T cells after adoptive transfer of CD4+ T-cell populations into an immunodeficient recipient.

journal_name

Scand J Immunol

journal_title

Scandinavian journal of immunology

authors

Rudolphi A,Enssle KH,Claesson MH,Reimann J

doi

10.1111/j.1365-3083.1993.tb01694.x

subject

Has Abstract

pub_date

1993-07-01 00:00:00

pages

57-64

issue

eissn

0300-9475

issn

1365-3083

journal_volume

pub_type

杂志文章

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Adoptive transfer of low numbers of CD4+ T cells into SCID mice chronically treated with soluble IL-4 receptor does not prevent engraftment of IL-4-producing T cells.