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Blood, Vol. 92 No. 11 (December 1), 1998:
pp. 4464-4471
Reconstitution of the T-Cell Compartment After Bone Marrow
Transplantation: Restoration of the Repertoire by Thymic Emigrants
Florence Dumont-Girard,
Etienne Roux,
René A. van Lier,
Geoff Hale,
Claudine Helg,
Bernard Chapuis,
Michel Starobinski, and
Eddy Roosnek
From the Division of Immunology, the Division of Oncology and the
Division of Hematology, the Department of Internal Medicine,
Hôpital Cantonal Universitaire, Geneva, Switzerland; the Lab for
Clinical Viro Immunology, CLB, Sanquin Bloodfoundation and Lab for
Experimental and Clinical Immunology, AMC, Amsterdam The Netherlands;
and the Sir William Dunn School of Pathology, University of Oxford,
Oxford, UK.
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/µL 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/µL. In the other
three patients, T cells remained low (87 ± 64 T cells/µL 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/µL) 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/µL). 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.
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