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

After intravenous injection of 105 purified, lymph node (LN)‐derived dm2 (H‐2d/Ld) CD4+ T cells into young C.B‐17 scidjscid (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 human 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 tr