Effect of IL-12 and soluble IL-4 receptor on the herpesvirus infection in human SCID chimeras whose Th2 cells predominate

Tatsushi Katakura, Makiko Kobayashi, David N. Herndon, Fujio Suzuki

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Th2 cytokines, commonly detected in burn patients, have been shown as inhibitors for the generation of Th1 cells that are essential for the host's resistance against herpes simplex virus type 1 (HSV-1) infection. In this study, the possibility of immunological treatment through the regulation of Th1/Th2 responses was examined in two kinds of human severe combined immunodeficiency (SCID) chimera models reflecting human immune functions. SCID mice injected with a mixture of PBMC from a healthy donor and Th2 cells experimentally generated from the same healthy PBMC (Th2 SCID chimeras) were more susceptible to HSV-1 infection when compared with SCID mice injected with healthy donor PBMC (healthy SCID chimeras). When Th2 SCID chimeras were individually treated with human IL-12 (hIL-12) or human soluble IL-4 receptor (hsIL-4R), hIFN-γ was not produced in their sera after antihuman CD3 mAb stimulation. However, hIFN-γ production in sera of Th2 SCID chimeras treated with the combination therapy of hIL-12 and hsIL-4R was recovered at levels observed in healthy SCID chimeras. When Th2 SCID chimeras infected with HSV-1 were treated with saline, hIL-12, hsIL-4R or a combination of hIL-12 and hsIL-4R, 13%, 13%, 25% or 100% of them survived, respectively. Also, Th1 responses (hIFN-γ production) were demonstrated in Th2 SCID chimeras that became resistant against HSV-1 infection after the combination treatment. These results suggest that individuals whose Th2 cells predominated may be immunologically controlled by the combination treatment between a Th1 response inducer and a Th2 response inhibitor.

Original languageEnglish (US)
Pages (from-to)421-426
Number of pages6
JournalImmunology and Cell Biology
Volume82
Issue number4
DOIs
StatePublished - Aug 1 2004

Keywords

  • Burn injury
  • Herpesvirus
  • IL-12
  • Soluble IL-4 receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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