T cell repertoire development in XSCID dogs following nonconditioned allogeneic bone marrow transplantation.

Abstract

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.

• Authors: William Vernau, Brian J Hartnett, Douglas R Kennedy, Peter F Moore, Paula S Henthorn, Kenneth I Weinberg, Peter J Felsburg
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 13 Issue 9 Pg. 1005-15 (Sep 2007) ISSN: 1083-8791 [Print] United States
• PMID: 17697962 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Receptors, Antigen, T-Cell

Topics

• Animals
• Bone Marrow Transplantation
• CD4-CD8 Ratio
• Dogs
• Follow-Up Studies
• Gene Rearrangement, T-Lymphocyte
• Hematopoiesis
• Receptors, Antigen, T-Cell (genetics)
• T-Lymphocytes (cytology, immunology)
• Transplantation, Homologous
• X-Linked Combined Immunodeficiency Diseases (therapy)