Requirement of residual thymus to restore normal T-cell subsets after human allogeneic bone marrow transplantation.
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.


CONCLUSIONS
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.
Heitger
A
A
University Children's Hospital Innsbruck, Austria. andreas.heitger@uibk.ac.at
Greinix
H
H
Mannhalter
C
C
Mayerl
D
D
Kern
H
H
Eder
J
J
Fink
F M
FM
Niederwieser
D
D
Panzer-Grümayer
E R
ER
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000473:pathology*; D013601:T-Lymphocytes / Q000637:transplantation; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000473:pathology; D013934:Thymectomy; D013950:Thymus Gland / Q000503:physiopathology*; D014019:Tissue Donors; D014184:Transplantation, Homologous
D011948:Receptors, Antigen, T-Cell; D017493:Leukocyte Common Antigens