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Development and function of T lymphocytes and natural killer cells after bone marrow transplantation of severely immunodeficient mice
Author(s) -
Wang Baoping,
Simpson Stephen J.,
Holländer Georg A.,
Terhorst Cox
Publication year - 1997
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.1600-065x.1997.tb00973.x
Subject(s) - transplantation , immunology , biology , progenitor cell , bone marrow , stromal cell , haematopoiesis , t cell , natural killer cell , stem cell , cancer research , microbiology and biotechnology , immune system , medicine , in vitro , cytotoxic t cell , biochemistry
Summary: Bone marrow (BM) transplantation experiments were performed in a strain of CD3E‐transgenii: mice, termed tge26, which are completely deficient in T‐cell and natural killer (NK) cell development. We found that an interaction of stromal cells and prothymocytes is required for the induction of a cortical thymic microenvironment. This induction takes place in a time window from fetal development to early neonates. Although the thymic environment is not required for NK‐cell development, we found that aberrantly educated αβ or γδ T lymphocytes can influence NK‐cell ontogeny. Surprisingly, BM transplantation of tge26 fetuses and neonates results in normal T‐cell development, but very low levels of NK cells. The poor NK‐cell reconstitution in fetal and neonatal stages could be explained by an inefficient migration of hematopoietic progenitor ceils to the BM. By contrast, migration of the progenitor cells to the thymus was efficient to initiate T‐cell development, BM transplantation of adult tgE26 mice resulted in abnormal T‐cell development which, in turn, caused an inflammatory bowel disease (IBD) in the recipient mice. Studies in these BM chimeras have revealed that both αβ and γδ T cells can be pathogenic and, further, that Th 1‐like cytokines produced by these cells are causal factors in the pathogenesis of IBD.