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Blood, 15 September 2002, Vol. 100, No. 6, pp. 2235-2242
TRANSPLANTATION
Direct evidence for new T-cell generation by patients
after either T-cell-depleted or unmodified allogeneic hematopoietic
stem cell transplantations
Sharon R. Lewin,
Glenn Heller,
Linqi Zhang,
Elaine Rodrigues,
Eva Skulsky,
Marcel R. M. van den
Brink,
Trudy N. Small,
Nancy A. Kernan,
Richard J. O'Reilly,
David D. Ho, and
James W. Young
From the Aaron Diamond AIDS Research Center, The
Rockefeller University; and the Department of Epidemiology and
Biostatistics, Allogeneic Bone Marrow Transplantation Service,
Departments of Pediatrics and Medicine, Memorial Sloan-Kettering Cancer
Center, New York, NY.
Successful allogeneic hematopoietic stem cell transplantation
(HSCT) requires reconstitution of normal T-cell immunity. Recipient thymic activity, biologic features of the allograft, and preparative regimens all contribute to immune reconstitution. We evaluated circulating T-cell phenotypes and T-cell receptor rearrangement excision circles (TRECs) in 331 blood samples from 158 patients who had
undergone allogeneic HSCTs. All patients had received myeloablative
conditioning regimens and were full donor chimeras in remission.
Younger patients exhibited more rapid recovery and higher TRECs
(P = .02). Recipients of T-cell-depleted allografts initially had lower TRECs than unmodified allograft recipients (P < .01), but the difference abated beyond 9 months.
TREC level disparities did not achieve significance among adults with
respect to type of allograft. Measurable, albeit low, TREC values
correlated strongly with severe opportunistic infections
(P < .01). This finding was most notable during the
first 6 months after transplantation, when patients are at greatest
risk but before cytofluorography can detect circulating
CD45RA+ T cells. Low TRECs also correlated strongly with
extensive chronic graft-versus-host disease (P < .01).
Recipients of all ages of either unmodified or T-cell-depleted
allografts therefore actively generate new T cells. This generation is
most notable among adult recipients of T-cell-depleted allografts,
most of whom had also received antithymocyte globulin for rejection
prophylaxis. Low TREC values are significantly associated with
morbidity and mortality after transplantation. T-cell neogenesis,
appropriate to age but delayed in adult recipients of
T-cell- depleted allografts, justifies interventions to hasten this
process and to stimulate desirable cellular immune responses.
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