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© Research
Publication : Blood

Limits of the human-PBL-SCID mice model: severe restriction of the V beta T-cell repertoire of engrafted human T cells

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Blood - 01 Jan 1997

Garcia S, Dadaglio G, Gougeon ML

Link to Pubmed [PMID] – 8978309

Blood 1997 Jan;89(1):329-36

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.

http://www.ncbi.nlm.nih.gov/pubmed/8978309