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Blood, Vol. 94 No. 10 (November 15), 1999:
pp. 3432-3438
Coexistence of Two Functioning T-Cell Repertoires in Healthy
Ex-Thalassemics Bearing a Persistent Mixed Chimerism Years After Bone
Marrow Transplantation
Manuela Battaglia,
Marco Andreani,
Marisa Manna,
Sonia Nesci,
Paola Tonucci,
Barbara Persini,
Gioacchino Robustelli della Cuna,
Arcangelo Nocera,
Jack Gorski,
Guido Lucarelli, and
Raffaele De Palma
From the Divisione di Ematologia e Centro Trapianto di Midollo
Osseo-Ospedale di Muraglia, Pesaro, Italy; the Lab di Medicina
Sperimentale, Fondazione "S. Maugeri," Pavia, Italy; the Sezione
di Immunologia, Ospedale S. Martino, Genova, Italy; The Blood Research
Institute, Milwaukee, WI; and the Dipartimento di Internistica Clinica
e Sperimentale, II Universita' di Napoli, Napoli, Italy.
Bone marrow transplantation (BMT) from an HLA-identical donor is an
established therapy to cure homozygous  -thalassemia. Approximately 10% of thalassemic patients developed a
persistent mixed chimerism (PMC) after BMT characterized by stable
coexistence of host and donor cells in all hematopoietic compartments.
Interestingly, in the erythrocytic lineage, close to normal levels of
hemoglobin can be observed in the absence of complete
donor engraftment. In the lymphocytic lineage, the striking feature is
the coexistence of immune cells. This implies a state of tolerance or
anergy, raising the issue of immunocompetence of the host. To
understand the state of the T cells in PMC, repertoire analysis and
functional studies were performed on cells from 3 ex-thalassemics.
Repertoire analysis showed a profound skewing. This was due to an
expansion of some T cells and not to a collapse of the repertoire,
because phytohemagglutinin stimulation showed the presence
of a complex repertoire. The immunocompetence of the chimeric immune
systems was further established by showing responses to
alloantigens and recall antigens in vitro. Both host and
donor lymphocytes were observed in the cultures. These data suggest
that the expanded T cells play a role in specific tolerance while
allowing a normal immune status in these patients.
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