TY - JOUR
T1 - T Cell Repertoire Development in XSCID Dogs Following Nonconditioned Allogeneic Bone Marrow Transplantation
AU - Vernau, William
AU - Hartnett, Brian J.
AU - Kennedy, Douglas R.
AU - Moore, Peter F
AU - Henthorn, Paula S.
AU - Weinberg, Kenneth I.
AU - Felsburg, Peter J.
PY - 2007/9
Y1 - 2007/9
N2 - 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 Vβ 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 Vβ 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.
AB - 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 Vβ 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 Vβ 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.
KW - Bone marrow transplants
KW - Dogs
KW - X-linked severe combined immunodeficiency
UR - http://www.scopus.com/inward/record.url?scp=34547699361&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34547699361&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2007.05.013
DO - 10.1016/j.bbmt.2007.05.013
M3 - Article
C2 - 17697962
AN - SCOPUS:34547699361
VL - 13
SP - 1005
EP - 1015
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
SN - 1083-8791
IS - 9
ER -