Coexistence of two functioning T cell repertoires in healthy ex-thalassemics with persistent mixed chimerism after bone marrow transplantation

M. Andreani, M. Manna, S. Nesci, P. Tonucci, B. Persini, R. Emiliani, R. De Palma, M. Donati, M. Battaglia, A. Nocera, J. Gorski, G. Lucarelli

Research output: Contribution to journalArticlepeer-review

Abstract

Bone Marrow Transplantation (BMT) from an HLA identical donor is an established therapy to cure homozygous b-thalassemia. Approximately ten percent of thalassemic transplanted patients developed a persistent mixed chirnerism (PMC) post-BMT, characterized by stable coexistence of host and donor cells for a period longer than 2 years. To better understand the immunological phenomena underlying the unexpected status found, we analyzed the T cell repertoire by means of TCR b-chain CDR3 spectratyping in 3 patients showing PMC with at least 30% residual host cells at three or more years post-transplant. Results The 3 patients analyzed as part of this study have normal lymphocytes counts with normal CD4/CD8 ratios and normal levels of Hb. Repertoire analysis of the PBMC from the three PMC patients showed severe alterations. Such a skewed repertoire was observed in almost all the TCR BV families from all three patients, with the presence of predominant peaks and the loss of the characteristic gaussian pattern. Such a profound skewing in T cell repertoire is compatible with a collapse of the repertoire and has been associated with severely compromised immune systems post-transplant. In contrast, the three patients were healthy and did not show any sign of a compromised immune system. To determine the complexity underlying of the predominant peaks observed in the peripheral blood, we performed single strand conformational polymorphism analysis (SSCP) on the DNA. This technique allows detection of single base pair differences in two DNA strands of the same size. We selected the prominent peaks present in different TCR BV families from each of the three patients for the SSCP analysis, BV 20 in UPN 855, BV2 in UPN 688 and BV 5.3, in UPN1074. In all cases, the predominant spectratype peaks could be resolved into one or two bands, while a smear was observed in the SSCP profile of single spectratype peak known to be polyclonal. After PHA stimulation, spectratype analysis of the cultures showed a normal repertoire pattern. Conclusions These data showed that preferential expansions of given T cell clonotypes were present in the peripheral blood of PMC patients and suggest that these expansions could correlate with the establishing of specific tolerance/anergy. The understanding of the steps required for establishing the PMC is of great importance and may contribute to improve the handling of allogeneic BMT. The establishing of PMC could lead to a reduction of the amount of drugs used for conditioning regimens and a lowering of the doses of immunosuppression administered before BMT, thus reducing the transplant related mortality.

Original languageEnglish
Pages (from-to)260
Number of pages1
JournalEuropean Journal of Immunogenetics
Volume28
Issue number2
Publication statusPublished - 2001

ASJC Scopus subject areas

  • Immunology
  • Genetics

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