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Blood, 15 September 2000, Vol. 96, No. 6, pp. 2299-2303
TRANSPLANTATION
Recovery of immune reactivity after T-cell-depleted bone marrow
transplantation depends on thymic activity
Etienne Roux,
Florence Dumont-Girard,
Michel Starobinski,
Claire-Anne Siegrist,
Claudine Helg,
Bernard Chapuis, and
Eddy Roosnek
From the Division of Immunology and Allergology,
Division of Oncology, and Division of Hematology, Department of
Internal Medicine; and Center for Vaccinology and Neonatal Immunology,
Department of Pathology and Pediatrics, University Hospital, Geneva,
Switzerland.
To evaluate the importance of the thymus for the reconstitution of
immunity in recipients of a T-cell-depleted bone marrow, we measured
the appearance of CD4+CD45RA+RO
naive T cells (thymic rebound), restoration of the diversity of the
T-cell-receptor (TCR) repertoire and the response to
vaccinations with tetanus toxoid (TT). Repopulation by
CD4+CD45RA+RO thymic emigrants
varied among patients, starting at approximately 6 months after
transplantation. Young patients reconstituted swiftly, whereas in older
patients, the recovery of normal numbers of naive CD4+ T
cells could take several years. Restoration of TCR diversity was
correlated with the number of naive
CD4+CD45RA+RO T cells. Moreover,
the extent of the thymic rebound correlated with the patient's
capacity to respond to vaccinations. Patients without a significant
thymic rebound at the moment of vaccination (CD4+CD45RA+RO T cells less than
30 µL) did not respond, or responded only marginally even after 3 boosts with TT. We conclude that during the first year after
transplantation, the absence of an immune response is due mainly to the
loss of an adequate T-cell repertoire. Restoration of the repertoire
can come only from a thymic rebound that can be monitored by measuring
the increase of CD4+CD45RA+RO
naive T cells. This will allow postponing revaccinations to a moment
when the patient will be able to respond more effectively. This may be
particularly useful in the elderly patient who, owing to low thymic
activity, might not yet be able to respond 1 year after
transplant when revaccinations are usually scheduled.
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