Journal article
Total lymphoid irradiation nonmyeloablative preconditioning enriches for IL-4–producing CD4+-TNK cells and skews differentiation of immunocompetent donor CD4+cells
Blood, Vol.101(5), pp.2024-2032
03/01/2003
DOI: 10.1182/blood-2002-05-1513
PMID: 12406908
Abstract
Preconditioning with the nonmyeloablative regimen total lymphoid irradiation (TLI) before hematopoietic cell transplantation facilitates the establishment of mixed chimerism and protects against graft-versus-host disease. We reported that the development of mixed chimerism requires interleukin (IL)–4 and is associated with increased host anti-donor TH2 cells, but the effect of TLI on the differentiation of immunocompetent donor cells has not been investigated. To examine the extent to which TLI preconditioning influences donor T cells, we measured responses of transgenic CD4+ cells specific for ovalbumin peptide (OVA-Tg) following in vivo and in vitro antigen stimulation in a TLI-preconditioned environment. OVA-Tg cells that were adoptively transferred into TLI-preconditioned mice that express cross-reactive antigens produced more IL-4 and less interferon-γ and IL-2 than controls when stimulated with OVA peptide one week later. OVA-Tg primed in vitro with spleen from TLI-preconditioned mice generated more TH2 and fewer TH1 cells when stimulated in recall enzyme-linked immunosorbent spot (ELISPOT) assays with OVA peptide. Naive OVA-Tg up-regulated CD69 and CD25 normally following stimulation with OVA peptide in the presence of spleen from TLI-preconditioned mice, but proliferated less and secreted less IL-2 than controls. Surprisingly, naive OVA-Tg secreted IL-4 in primary cultures that were stimulated with OVA peptide in the presence of spleen from TLI-preconditioned mice. This response depends on CD4+ cells from TLI-spleen, which constitutively produce IL-4 and are composed primarily of CD4+–natural killer T (TNK) cells. Thus, TLI preconditioning enriches for IL-4–secreting and TNK-like CD4+ cells that may function in the protection from graft-versus-host disease by redirecting the differentiation of immunocompetent donor CD4+ cells toward TH2 and away from pathogenic TH1 cells.
Details
- Title: Subtitle
- Total lymphoid irradiation nonmyeloablative preconditioning enriches for IL-4–producing CD4+-TNK cells and skews differentiation of immunocompetent donor CD4+cells
- Creators
- Shawn M Rigby - From the Department of Internal Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City; and the Department of Veterans Affairs Medical Center, Iowa City, IATodd Rouse - From the Department of Internal Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City; and the Department of Veterans Affairs Medical Center, Iowa City, IAElizabeth H Field - From the Department of Internal Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City; and the Department of Veterans Affairs Medical Center, Iowa City, IA
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.101(5), pp.2024-2032
- DOI
- 10.1182/blood-2002-05-1513
- PMID
- 12406908
- NLM abbreviation
- Blood
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Language
- English
- Date published
- 03/01/2003
- Academic Unit
- Immunology; Internal Medicine
- Record Identifier
- 9984094641302771
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