| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
Departments of
*
Immunology,
Medicine, and
Pediatrics, Duke University Medical Center, Durham, NC 27710
Transplantation of HLA-identical or haploidentical T cell-depleted allogeneic bone marrow (BM) into SCID infants results in thymus-dependent T cell development in the recipients. Immunoscope analysis of the TCR V
repertoire was performed on 15 SCID patients given BM transplants. Before and within the first 100 days after bone marrow transplantation (BMT), patients’ PBMC displayed an oligoclonal or skewed T cell repertoire, low TCR excision circles (TREC) values, and a predominance of CD45RO+ T cells. In contrast, the presence of high numbers of CD45RA+ cells in the circulation of SCID patients >100 days post-BMT correlated with active T cell output by the thymus as revealed by high TREC values and a polyclonal T cell repertoire demonstrated by a Gaussian distribution of V-specific peaks. Ten years after BMT, we observed a decrease of the normal polyclonal T cell repertoire and an increase of a more skewed T cell repertoire. A decline of TREC levels and a decrease in the number of CD45RA+ cells beyond 10 years after BMT was concomitant with the detection of oligoclonal CD3+CD8+CD45RO+ cells. The switch from a polyclonal to a more skewed repertoire, observed in the CD3+CD8+CD45RO+ T cell subset, is a phenomenon that occurs normally with decreased thymic output during aging, but not as rapidly as in this patient population. We conclude that a normal T cell repertoire develops in SCID patients as a result of thymic output and the repertoire remains highly diverse for the first 10 years after BMT. The TCR diversity positively correlates in these patients with TREC levels.
This article has been cited by other articles:
|
|
 |
|
  M. Sarzotti-Kelsoe, C. M. Win, R. E. Parrott, M. Cooney, B. K. Moser, J. L. Roberts, G. D. Sempowski, and R. H. Buckley Thymic output, T-cell diversity, and T-cell function in long-term human SCID chimeras Blood, August 13, 2009; 114(7): 1445 - 1453. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A R Lorenzi, T A Morgan, A Anderson, J Catterall, A M Patterson, H E Foster, and J D Isaacs Thymic function in juvenile idiopathic arthritis Ann Rheum Dis, June 1, 2009; 68(6): 983 - 990. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Vrisekoop, R. van Gent, A. B. de Boer, S. A. Otto, J. C. C. Borleffs, R. Steingrover, J. M. Prins, T. W. Kuijpers, T. F. W. Wolfs, S. P. M. Geelen, et al. Restoration of the CD4 T Cell Compartment after Long-Term Highly Active Antiretroviral Therapy without Phenotypical Signs of Accelerated Immunological Aging J. Immunol., July 15, 2008; 181(2): 1573 - 1581. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Czechowicz, D. Kraft, I. L. Weissman, and D. Bhattacharya Efficient Transplantation via Antibody-Based Clearance of Hematopoietic Stem Cell Niches Science, November 23, 2007; 318(5854): 1296 - 1299. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Chinen, J. Davis, S. S. De Ravin, B. N. Hay, A. P. Hsu, G. F. Linton, N. Naumann, E. Y. H. Nomicos, C. Silvin, J. Ulrick, et al. Gene therapy improves immune function in preadolescents with X-linked severe combined immunodeficiency Blood, July 1, 2007; 110(1): 67 - 73. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Cavazzana-Calvo, F. Carlier, F. Le Deist, E. Morillon, P. Taupin, D. Gautier, I. Radford-Weiss, S. Caillat-Zucman, B. Neven, S. Blanche, et al. Long-term T-cell reconstitution after hematopoietic stem-cell transplantation in primary T-cell-immunodeficient patients is associated with myeloid chimerism and possibly the primary disease phenotype Blood, May 15, 2007; 109(10): 4575 - 4581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Roberts, J. P. H. Lauritsen, M. Cooney, R. E. Parrott, E. O. Sajaroff, C. M. Win, M. D. Keller, J. H. Carpenter, J. Carabana, M. S. Krangel, et al. T-B+NK+ severe combined immunodeficiency caused by complete deficiency of the CD3{zeta} subunit of the T-cell antigen receptor complex Blood, April 15, 2007; 109(8): 3198 - 3206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Borghans, R. G. Bredius, M. D. Hazenberg, H. Roelofs, E. C. Jol-van der Zijde, J. Heidt, S. A. Otto, T. W. Kuijpers, W. E. Fibbe, J. M. Vossen, et al. Early determinants of long-term T-cell reconstitution after hematopoietic stem cell transplantation for severe combined immunodeficiency Blood, July 15, 2006; 108(2): 763 - 769. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Neff, B. C. Beard, and H.-P. Kiem Survival of the fittest: in vivo selection and stem cell gene therapy Blood, March 1, 2006; 107(5): 1751 - 1760. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Adjali, R. R. Vicente, C. Ferrand, C. Jacquet, C. Mongellaz, P. Tiberghien, K. Chebli, V. S. Zimmermann, and N. Taylor Intrathymic administration of hematopoietic progenitor cells enhances T cell reconstitution in ZAP-70 severe combined immunodeficiency PNAS, September 20, 2005; 102(38): 13586 - 13591. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. He, J. K. Tomfohr, B. H. Devlin, M. Sarzotti, M. L. Markert, and T. B. Kepler SpA: web-accessible spectratype analysis: data management, statistical analysis and visualization Bioinformatics, September 15, 2005; 21(18): 3697 - 3699. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. B. Kepler, M. He, J. K. Tomfohr, B. H. Devlin, M. Sarzotti, and M. L. Markert Statistical analysis of antigen receptor spectratype data Bioinformatics, August 15, 2005; 21(16): 3394 - 3400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Thrasher, S. Hacein-Bey-Abina, H. B. Gaspar, S. Blanche, E. G. Davies, K. Parsley, K. Gilmour, D. King, S. Howe, J. Sinclair, et al. Failure of SCID-X1 gene therapy in older patients Blood, June 1, 2005; 105(11): 4255 - 4257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Schmidt, S. Hacein-Bey-Abina, M. Wissler, F. Carlier, A. Lim, C. Prinz, H. Glimm, I. Andre-Schmutz, C. Hue, A. Garrigue, et al. Clonal evidence for the transduction of CD34+ cells with lymphomyeloid differentiation potential and self-renewal capacity in the SCID-X1 gene therapy trial Blood, April 1, 2005; 105(7): 2699 - 2706. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
