Apoptotic cells and clonally expanded cytotoxic T cells in bone marrow trephines of patients with myelodysplastic syndrome.
OBJECTIVE
There is increasing evidence that autoimmunity is involved in the pathogenesis of myelodysplastic syndromes (MDS). We examined the number of apoptotic cells, and analysed the T cells and the T cell receptor gene rearrangements in bone marrow trephines of patients with low-grade MDS [refractory anaemia (RA), refractory anaemia with ringed sideroblasts (RAS) and refractory cytopenia with multilineage dysplasia (RCMD)] to investigate the correlation between T cells and apoptosis.


RESULTS
Bone marrow trephines from 30 patients with RA, seven patients with RCMD, four patients with RAS and 11 normal bone marrow donors were stained for CD3 and for apoptotic cells using immunohistochemistry and terminal deoxynucleotidyl transferase 2'-deoxyuridine, 5'-triphosphate (dUTP) nick end labelling (TUNEL) technique, respectively. The positive cells were quantified by computer-assisted image analysis. In addition, CD 8 and T cell-restricted intracellular antigen-1 (TIA-1)-positive cells were analysed by single staining and evaluated semiquantitatively by light microscopy. Junctional diversity of the T cell receptor (TCR) α-, β- and γ-chains were analysed in 24 cases of RA and RCMD by reverse transcription-polymerase chain reaction (RT-PCR). In all cases of RA, RCMD and RAS an increase of apoptotic cells was accompanied by an increase of T cells, when compared to normal donors (P < 0.001). Expression of TIA-1 was found in 33 of 41 patients with low-grade MDS. In contrast, normal controls showed either no or only very weak expression. Furthermore, 14 of 24 cases with low-grade MDS showed clonal TCR gene rearrangement.


CONCLUSIONS
These findings provide evidence that increased apoptosis in low-grade MDS correlates with increased numbers of cytotoxic T cells. A considerable proportion of the MDS cases showed clonal TCR rearrangement suggesting an antigen-driven selection of the T cells. We therefore speculate that cases of MDS can be accompanied by a presumably autoreactive T cell-mediated apoptosis induction in bone marrow cells.
Institute of Pathology, University of Erlangen-Nuremberg, Erlangen, Germany.
Heinke
H
Pülhorn
Martin
M
Herrmann
Harry
H
Harms
Andreas
A
Jung
Irith
I
Baumann
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000753:Anemia, Refractory / Q000235:genetics / Q000276:immunology / Q000473:pathology; D000754:Anemia, Refractory, with Excess of Blasts / Q000235:genetics / Q000276:immunology / Q000473:pathology; D017209:Apoptosis / Q000276:immunology*; D015551:Autoimmunity; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D006801:Humans; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology*
D017931:DNA Primers