T cell repertoire development in XSCID dogs following nonconditioned allogeneic bone marrow transplantation.
Dogs with X-linked severe combined immunodeficiency (XSCID) can be successfully treated by bone marrow transplants (BMT) resulting in full immunologic reconstitution and engraftment of both donor B and T cells without the need for pretransplant conditioning. In this study, we evaluated the T cell diversity in XSCID dogs 4 months to 10.5 years following BMT. At 4 months posttransplantation, when the number of CD45RA+ (naïve) T cells had peaked and plateaued, the T cells in the transplanted dogs showed the same complex, diverse repertoire as those of normal young adult dogs. A decline in T cell diversity became evident approximately 3.5 years posttransplant, but the proportion of Vbeta families showing a polyclonal Gaussian spectratype still predominated up to 7.5 years posttransplant. In 2 dogs evaluated at 7.5 and 10.5 years posttransplant, >75% of the Vbeta families consisted of a skewed or oligoclonal spectratype that was associated with a CD4/CD8 ratio of <0.5. The decline in the complexity of T cell diversity in the transplanted XSCID dogs is similar to that reported for XSCID patients following BMT. However, in contrast to transplanted XSCID boys who show a significant decline in their T cell diversity by 10 to 12 years following BMT, transplanted XSCID dogs maintain a polyclonal, diverse T cell repertoire through midlife.
Vernau
William
W
Department of Veterinary Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, California, USA.
Hartnett
Brian J
BJ
Kennedy
Douglas R
DR
Moore
Peter F
PF
Henthorn
Paula S
PS
Weinberg
Kenneth I
KI
Felsburg
Peter J
PJ
D000818:Animals; D016026:Bone Marrow Transplantation; D016516:CD4-CD8 Ratio; D004285:Dogs; D005500:Follow-Up Studies; D015329:Gene Rearrangement, T-Lymphocyte; D006410:Hematopoiesis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014184:Transplantation, Homologous; D053632:X-Linked Combined Immunodeficiency Diseases / Q000628:therapy*
D011948:Receptors, Antigen, T-Cell
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