Cells of Th2 cytokine phenotype prevent LPS-lnduced lethality during murine graft-versus-host reaction

Regulation of cytokines and CD8+ lymphoid engraftment

Daniel H. Fowler, Kazuhiro Kurasawa, Anne Husebekk, Peter A Cohen, Ronald E. Gress

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

A murine parent-into-F1 graft-vs-host reaction (GVHR) model that utilizes LPS to induce lethality was used to evaluate the in vivo regulatory role of donor cells of Th2 cytokine phenotype. Transfer of B6 spleen cells into B6C3F1 hosts was lethal when LPS endotoxin (15 μg) was administered on day 7 after cell transfer. Parental cells of Th2 cytokine phenotype were generated by treating B6 mice in vivo with a combination of IL-2 and IL-4 or with high dose IL-2. The CD4-enriched population from these cytokine-treated mice expressed and secreted increased levels of IL-4 and IL-10, with concomitantly decreased IL-2 and IFN-γ. Cell mixing experiments (parental spleen cells + parental CD4-enriched, Th2-type cells) demonstrated that the Th2-type cells protected F1 hosts from LPS-induced lethality. These mice were analyzed to study possible mechanisms by which this protection was mediated. Compared with mice undergoing LPS-induced lethality during GVHR, Th2-protected mice had: 1) lower levels of donor CD8+ lymphoid engraftment, 2) in vivo suppression of IFN-γ mRNA, 3) in vivo augmentation of IL-4 mRNA, and 4) a reduction in serum TNF-α. We thus conclude that donor cells of Th2 cytokine phenotype prevent LPS-induced, TNF-a-mediated lethality during GVHR, and that this protection is associated with regulation of both cellular- and cytokine-mediated events. As a result, we propose that cells of Th2 cytokine phenotype may represent a novel approach for establishing allogeneic lymphoid engraftment without lethal graft-vs-host disease.

Original languageEnglish (US)
Pages (from-to)1004-1013
Number of pages10
JournalJournal of Immunology
Volume152
Issue number3
StatePublished - Feb 1 1994
Externally publishedYes

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Th2 Cells
Graft vs Host Reaction
Cytokines
Transplants
Phenotype
Interleukin-4
Interleukin-2
Spleen
Messenger RNA
Graft vs Host Disease
Endotoxins
Interleukin-10
Serum
Population

ASJC Scopus subject areas

  • Immunology

Cite this

Cells of Th2 cytokine phenotype prevent LPS-lnduced lethality during murine graft-versus-host reaction : Regulation of cytokines and CD8+ lymphoid engraftment. / Fowler, Daniel H.; Kurasawa, Kazuhiro; Husebekk, Anne; Cohen, Peter A; Gress, Ronald E.

In: Journal of Immunology, Vol. 152, No. 3, 01.02.1994, p. 1004-1013.

Research output: Contribution to journalArticle

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