Dendritic cells of immune thrombocytopenic purpura (ITP) show increased capacity to present apoptotic platelets to T lymphocytes.
OBJECTIVE
Altered self-antigen processing/presentation of apoptotic cells by DCs and/or modifications of autoantigens may lead to the development of autoantibodies. Increasing evidence indicates that platelets may undergo apoptosis. Therefore, in the present study we investigated whether platelet apoptosis and/or dendritic cells (DCs) may play a role in the stimulation of the immuno-mediated anti-platelet response in chronic immune thrombocytopenic purpura (ITP).


RESULTS
Twenty-nine patients with active ITP and 29 healthy adult volunteers were enrolled into the study. Freshly washed platelets and platelets aged in a plasma-free buffer for 72 hours at 37 degrees C were assessed by flow cytometry for phosphatidylserine exposure using annexin V-FITC, caspase activation, and platelet activation markers. CD14-derived DCs were characterized by immunophenotyping, cytokine production, and ability to present fresh and aged platelets to T lymphocytes. We demonstrated that platelets from ITP patients, either fresh or in vitro aged, show increased apoptosis (with low levels of activation) in comparison to their normal counterparts. We also found that immature DCs readily ingest apoptotic platelets. Furthermore, in ITP patients DCs, prepulsed with autologous/allogeneic fresh and aged platelets, are highly efficient in stimulating autologous T-cell proliferation as compared to DCs derived from healthy donors. This finding may be related to the upregulated expression of CD86 in DCs from ITP patients and not to higher phagocytic activity.


CONCLUSIONS
These results suggest that DC dysfunction, together with increased propensity of platelets to undergo apoptosis, may play a role in the stimulation of the immune system in ITP.
Catani
Lucia
L
Istituto di Ematologia e Oncologia Medica L. e A. Seràgnoli, Università di Bologna, Bologna, Italy. lcatani@med.unibo.it
Fagioli
Maria Elena
ME
Tazzari
Pier Luigi
PL
Ricci
Francesca
F
Curti
Antonio
A
Rovito
Manuela
M
Preda
Paola
P
Chirumbolo
Gabriella
G
Amabile
Marilina
M
Lemoli
Roberto M
RM
Tura
Sante
S
Conte
Roberto
R
Baccarani
Michele
M
Vianelli
Nicola
N
D000328:Adult; D000368:Aged; D017209:Apoptosis; D001792:Blood Platelets / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*