Development and function of T lymphocytes and natural killer cells after bone marrow transplantation of severely immunodeficient mice.
Bone marrow (BM) transplantation experiments were performed in a strain of CD3 epsilon-transgenic mice, termed tg epsilon 26, 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 alpha beta or gamma delta T lymphocytes can influence NK-cell ontogeny. Surprisingly, BM transplantation of tg epsilon 26 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 cells to the BM. By contrast, migration of the progenitor cells to the thymus was efficient to initiate T-cell development. BM transplantation of adult tg epsilon 26 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 alpha beta and gamma delta T cells can be pathogenic and, further, that Th1-like cytokines produced by these cells are causal factors in the pathogenesis of IBD.
Wang
B
B
Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachussetts 02215, USA. bwang@bidmc.harvard.edu
Simpson
S J
SJ
Holländer
G A
GA
Terhorst
C
C
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000276:immunology* / Q000473:pathology* / Q000628:therapy; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology*