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Limits of the human-PBL-SCID mice model: severe restriction of the V beta
T-cell repertoire of engrafted human T cells
S Garcia, G Dadaglio and ML Gougeon
Departement SIDA et Retrovirus, Institut Pasteur, Paris, France.
A recent study in the human-peripheral blood lymphocytes severe combined
immunodeficiency (hu-PBL-SCID) model, analyzing the specificity of the
engrafted human T cells, showed that human T-cell lines and clones derived
from engrafted cells presented a xenoreactivity toward murine host
molecules. This observation raised the question of the influence of the
SCID environment on the ex vivo repertoire and function on the human T
cells reconstituting the murine host. We have characterized the human V
beta repertoire in the spleen of hu-PBL-SCID mice 1 to 3 months after their
engraftment. Fluorescence- activated cell sorting (FACS) analysis of human
V beta T-cell representation showed that, for all chimeras, all tested V
beta subsets were submitted to underrepresentation and/or expansion upon
engraftment. Importantly, these quantitative modifications of the T- cell
repertoire were associated with a severe restriction in both the CDR3 size
distribution pattern of the V beta transcripts and the number of J beta
segments used by these transcripts. In addition, ex vivo phenotypic
characterization of engrafted cells showed that 70% to 100% expressed the
activation markers HLA-DR, CD45RO, and CD38. Taken together, these results
suggest that, following their engraftment, human T cells were submitted to
a massive antigenic selection. Moreover, we found that these activated T
cells were unresponsive to in vitro mitogenic and superantigenic
activation. The consequences of the skewed repertoire and altered function
of engrafted human T cells on the validity of this humanized murine model
are discussed.
Volume 89,
Issue 1,
pp. 329-336,
01/01/1997
Copyright © 1997 by The American Society of Hematology
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