Reconstitution of the T-cell compartment after bone marrow transplantation: restoration of the repertoire by thymic emigrants.
We have studied the reconstitution of the T-cell compartment after bone marrow transplantation (BMT) in five patients who received a graft-versus-host disease (GVHD) prophylaxis consisting of methotrexate, cyclosporin, and 10 daily injections (day -4 to day +5) of Campath-1G. This treatment eliminated virtually all T cells (7 +/- 8 T cells/microL at day 14) which facilitated the analysis of the thymus-dependent and independent pathways of T-cell regeneration. During the first 6 months, the peripheral T-cell pool was repopulated exclusively through expansion of residual T cells with all CD4(+) T cells expressing the CD45RO-memory marker. In two patients, the expansion was extensive and within 2 months, the total number of T cells (CD8>>CD4) exceeded 1,000/microL. In the other three patients, T cells remained low (87 +/- 64 T cells/microL at 6 months) and remained below normal values during the 2 years of the study. In all patients, the first CD4(+)CD45RA+RO- T cells appeared after 6 months and accumulated thereafter. In the youngest patient (age 13), the increase was relatively fast and naive CD4(+) T cells reached normal levels (600 T cells/microL) 1 year later. In the four adult patients (age 25 +/- 5), the levels reached at that time-point were significantly lower (71 +/- 50 T cells/microL). In all patients, the T-cell repertoire that had been very limited, diversified with the advent of the CD4(+)CD45RA+RO- T cells. Cell sorting experiments showed that this could be attributed to the complexity of the T-cell repertoire of the CD4(+)CD45RA+RO- T cells that was comparable to that of a normal individual and that, therefore, it is likely that these cells are thymic emigrants. We conclude that after BMT, the thymus is essential for the restoration of the T-cell repertoire. Because the thymic activity is restored with a lag time of approximately 6 months, this might explain why, in particular in recipients of a T-cell-depleted graft, immune recovery is delayed.
Dumont-Girard
F
F
Division of Immunology, the Division of Oncology and the Division of Hematology, the Department of Internal Medicine, Hôpital Cantonal Universitaire, Geneva, Switzerland.
Roux
E
E
van Lier
R A
RA
Hale
G
G
Helg
C
C
Chapuis
B
B
Starobinski
M
M
Roosnek
E
E
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D002465:Cell Movement / Q000276:immunology; D006086:Graft vs Host Disease / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000628:therapy*; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*; D014181:Transplantation Immunology
D007166:Immunosuppressive Agents