Natural killer cell development is blocked in the context of aberrant T lymphocyte ontogeny

Baoping Wang, Georg A. Holländer, Aliki Nichogiannopoulou, Stephen J. Simpson, Jordan S. Orange, Jose Carlos Gutierrez-Ramos, Steven J. Burakoff, Christine A. Biron, Cox Terhorst

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Over-expression of human or mouse CD3-ε transgenes profoundly disturbs T lymphocyte and natural killer (NK) cell development. One of these transgenic strains, termed tgε26, displays a very early block in T lymphocyte and NK cell development. We showed previously that the absence of early thymocyte progenitors results in an abnormal thymic microenvironment. Due to this thymic defect, T cell development could not be restored by bone marrow (BM) transplantation in adult tgε26 mice but could in fetal tgε26 mice. Here we examine the effect of this abnormal thymic environment on NK cell development. We demonstrate that NK cell maturation in tgε26 mice was reconstituted by BM derived from completely T cell-deficient mice, i.e. RAG-2(-/-) and TCRβ x δ(-/-), but not from wild-type mice. Moreover, tgε26 mice transplanted with BM from partially T cell-deficient mice, i.e. TCRα(-/-), TCRβ(-/-) and TCRδ(-/-) mice, did not reconstitute their NK cell compartment. We conclude from these studies that the thymic environment is not required for NK cell development, but that aberrantly educated αβ or γδ T lymphocytes can influence NK cell ontogeny. Furthermore, high serum levels of tumor necrosis factor (TNF) were detected in the vast majority of tgε26 mice transplanted with BM cells derived from partially T cell-deficient mice, but never from tgε26 mice transplanted with BM cells derived from completely T cell-deficient mice. The high levels of TNF may play an important role in the observed inhibition of NK cell development, since in vivo treatment with an anti-TNF antibody restored NK cell development.

Original languageEnglish
Pages (from-to)939-949
Number of pages11
JournalInternational Immunology
Volume8
Issue number6
DOIs
StatePublished - 1996
Externally publishedYes

Keywords

  • Bone marrow transplantation
  • Thymus
  • Tumor necrosis factor
  • tgε26 mice

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