Disturbed apoptosis of T-cells in patients with active idiopathic thrombocytopenic purpura.
Idiopathic thrombocytopenic purpura (ITP) is an organ specific autoimmune disorder in which T-lymphocyte abnormalities have pathogenetic importance. In a DNA microarray screen of CD3+ T-lymphocytes from ITP patients and healthy controls we found an altered expression of genes associated with apoptosis, e.g. A20, caspase-8 and Bax. This together with our previous findings of increased gene expression of Fas, interferon-g and IL-2 receptor beta (IL2RB) indicated an altered activation induced cell death (AICD) of T-cells in ITP. Using a proliferation assay we found that CD3+ lymphocytes from ITP patients were significantly more resistant to dexamethasone induced suppression compared to normal lymphocytes. We also found that cultured CD3+ lymphocytes from ITP patients in remission were more susceptible to apoptosis both in the presence and absence of dexamethasone compared to cells from patient with active ITP and healthy controls, as indicated by increased staining of AnnexinV binding. Our findings suggest that apoptotic resistance of activated T-lymphocytes in patients with active ITP may lead to defective clearance of autoreactive T-lymphocytes through AICD, which might cause a continued immune destruction of platelets. Conversely, a loss of resistance to AICD in ITP patients in remission might be an important mechanism for the achievement of remission.
Olsson
Bob
B
Haematology Section, Department of Internal Medicine, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden. bob.olsson@medic.gu.se
Andersson
Per-Ola
PO
Jacobsson
Stefan
S
Carlsson
Lena
L
Wadenvik
Hans
H
D000328:Adult; D017209:Apoptosis / Q000235:genetics*; D015551:Autoimmunity; D017252:CD3 Complex; D016022:Case-Control Studies; D049109:Cell Proliferation; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000209:etiology / Q000276:immunology*; D012074:Remission Induction; D016176:T-Lymphocyte Subsets; D013601:T-Lymphocytes / Q000473:pathology*
D017252:CD3 Complex; D003907:Dexamethasone