BACKGROUND: To determine the effect of residual thymic activity in reconstituting the T-cell system after T cell-depleting therapy, we monitored T-cell subsets of a unique thymectomized cancer patient in comparison to thymus-bearing patients after allogeneic bone marrow transplantation (BMT). METHODS: T cells and T-cell subsets previously shown in murine studies to be regulated by the thymus were analyzed by FACS from 6 to >48 months after BMT. The investigation of thymus-bearing patients included 32 examinations of 9 children and 14 adults. None of the investigated cases had severe graft-versus-host disease or severe infections when examined. RESULTS: In the thymectomized host, T-cell regeneration occurred by donor cell expansion and was characterized by two prominent features: (i) a persistent failure to regenerate naive (CD45RA+) T-helper cells (14%, median), consistent with the recently developed concept of a thymus-dependency; and (ii) persistently elevated proportions of CD3+CD4-CD8- cells (double-negative cells, median 29%), which were identified in T cell receptor (TCR)gamma delta+ (22%, median of CD3+ cells, 88% double negatives) but also TCRalpha beta+ T-cell populations (78%, median of CD3+ cells, 17% double negatives). In thymus-bearing patients, 10 of 12 and 6 of 14 examinations of children and adults, respectively, performed later than 12 months after BMT showed the proportion of CD4+CD45RA+ cells appropriate for age (>52% and >28% in children and adults, respectively). Elevated double-negative cells (>10%) were found in only three patients, but none had elevated double-negative cells with a TCRalpha beta+ phenotype. CONCLUSION: Residual thymic activity might, in addition to its well-established role for regenerating naive T-helper (CD4+CD45RA+) cells, control the expansion of double-negative cells. A normal T-cell subset regeneration in a proportion of thymus-bearing adult hosts indicates the potential of an effective residual thymic activity even beyond childhood.
BACKGROUND: To determine the effect of residual thymic activity in reconstituting the T-cell system after T cell-depleting therapy, we monitored T-cell subsets of a unique thymectomized cancerpatient in comparison to thymus-bearing patients after allogeneic bone marrow transplantation (BMT). METHODS: T cells and T-cell subsets previously shown in murine studies to be regulated by the thymus were analyzed by FACS from 6 to >48 months after BMT. The investigation of thymus-bearing patients included 32 examinations of 9 children and 14 adults. None of the investigated cases had severe graft-versus-host disease or severe infections when examined. RESULTS: In the thymectomized host, T-cell regeneration occurred by donor cell expansion and was characterized by two prominent features: (i) a persistent failure to regenerate naive (CD45RA+) T-helper cells (14%, median), consistent with the recently developed concept of a thymus-dependency; and (ii) persistently elevated proportions of CD3+CD4-CD8- cells (double-negative cells, median 29%), which were identified in T cell receptor (TCR)gamma delta+ (22%, median of CD3+ cells, 88% double negatives) but also TCRalpha beta+ T-cell populations (78%, median of CD3+ cells, 17% double negatives). In thymus-bearing patients, 10 of 12 and 6 of 14 examinations of children and adults, respectively, performed later than 12 months after BMT showed the proportion of CD4+CD45RA+ cells appropriate for age (>52% and >28% in children and adults, respectively). Elevated double-negative cells (>10%) were found in only three patients, but none had elevated double-negative cells with a TCRalpha beta+ phenotype. CONCLUSION: Residual thymic activity might, in addition to its well-established role for regenerating naive T-helper (CD4+CD45RA+) cells, control the expansion of double-negative cells. A normal T-cell subset regeneration in a proportion of thymus-bearing adult hosts indicates the potential of an effective residual thymic activity even beyond childhood.
Authors: Simona W Rossi; Lukas T Jeker; Tomoo Ueno; Sachiyo Kuse; Marcel P Keller; Saulius Zuklys; Andrei V Gudkov; Yousuke Takahama; Werner Krenger; Bruce R Blazar; Georg A Holländer Journal: Blood Date: 2007-01-09 Impact factor: 22.113
Authors: Mathias M Hauri-Hohl; Marcel P Keller; Jason Gill; Katrin Hafen; Esther Pachlatko; Thomas Boulay; Annick Peter; Georg A Holländer; Werner Krenger Journal: Blood Date: 2007-01-09 Impact factor: 22.113
Authors: G Andreola; M Chittenden; J Shaffer; A B Cosimi; T Kawai; P Cotter; S A Locascio; T Morokata; B R Dey; N T Tolkoff-Rubin; F Preffer; T Bonnefoix; K Kattleman; T R Spitzer; D H Sachs; M Sykes Journal: Am J Transplant Date: 2011-06 Impact factor: 8.086
Authors: Yoshiaki Nishimura; Tatsuhiko Igarashi; Alicia Buckler-White; Charles Buckler; Hiromi Imamichi; Robert M Goeken; Wendy R Lee; Bernard A P Lafont; Russ Byrum; H Clifford Lane; Vanessa M Hirsch; Malcolm A Martin Journal: J Virol Date: 2006-11-08 Impact factor: 5.103
Authors: Persis J Amrolia; Giada Muccioli-Casadei; Helen Huls; Stuart Adams; April Durett; Adrian Gee; Eric Yvon; Heidi Weiss; Mark Cobbold; H Bobby Gaspar; Cliona Rooney; Ingrid Kuehnle; Victor Ghetie; John Schindler; Robert Krance; Helen E Heslop; Paul Veys; Ellen Vitetta; Malcolm K Brenner Journal: Blood Date: 2006-06-01 Impact factor: 22.113