FAS-L, IL-10, and double-negative CD4 CD8 TCR / T cells are reliable markers of autoimmune lymphoproliferative syndrome (ALPS) associated with FAS loss of function
نویسندگان
چکیده
Aude Magerus-Chatinet,1,2 Marie-Claude Stolzenberg,1,2 Maria S. Loffredo,1,2 Bénédicte Neven,1-3 Catherine Schaffner,1,2 Nicolas Ducrot,1,2 Peter D. Arkwright,4 Brigitte Bader-Meunier,3 José Barbot,5 Stéphane Blanche,3 Jean-Laurent Casanova,2,3,6 Marianne Debré,3 Alina Ferster,7 Claire Fieschi,8 Benoit Florkin,9 Claire Galambrun,10 Olivier Hermine,2-3,11 Olivier Lambotte,12 Eric Solary,13 Caroline Thomas,14 Francoise Le Deist,15 Capucine Picard,2,3,16 Alain Fischer,1-3 and Frédéric Rieux-Laucat1,2
منابع مشابه
IL-17 protects T cells from apoptosis and contributes to development of ALPS-like phenotypes.
In autoimmune/lymphoproliferative syndrome (ALPS), defective Fas death receptor function causes lymphadenomegaly/splenomegaly, the expansion of T-cell receptor αβ(+) CD4/CD8 double-negative T cells, and frequent development of hematologic autoimmunity. Dianzani autoimmune lymphoproliferative disease (DALD) has a similar phenotype but lacks the expansion of double-negative T cells. This work sho...
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Accumulation of CD3(+) T-cell receptor (TCR)αβ(+)CD4(-)CD8(-) double-negative T cells (DNT) is a hallmark of autoimmune lymphoproliferative syndrome (ALPS). DNT origin and differentiation pathways remain controversial. Here we show that human ALPS DNT have features of terminally differentiated effector memory T cells reexpressing CD45RA(+) (TEMRA), but are CD27(+)CD28(+)KLRG1(-) and do not expr...
متن کاملNatural history of autoimmune lymphoproliferative syndrome associated with FAS gene mutations.
Autoimmune lymphoproliferative syndrome (ALPS) presents in childhood with nonmalignant lymphadenopathy and splenomegaly associated with a characteristic expansion of mature CD4 and CD8 negative or double negative T-cell receptor αβ(+) T lymphocytes. Patients often present with chronic multilineage cytopenias due to autoimmune peripheral destruction and/or splenic sequestration of blood cells an...
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Patients with autoimmune lymphoproliferative syndrome (ALPS) and lymphoproliferation (LPR) mice are deficient in Fas, and accumulate large numbers of αβ-TCR(+), CD4(-), CD8(-) double negative (DN) T cells. The function of these DN T cells remains largely unknown. The common γ subunit of the activating Fc receptors, FcRγ, plays an important role in mediating innate immune responses. We have show...
متن کاملDominant interfering fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome
Five unrelated children are described with a rare autoimmune lymphoproliferative syndrome (ALPS) characterized by massive nonmalignant lymphadenopathy, autoimmune phenomena, and expanded populations of TCR-CD3+CD4-CD8- lymphocytes. These findings, suggesting a genetic defect in the ability of T lymphocytes to respond to normal immunoregulatory mechanisms, prompted an evaluation of lymphocyte ap...
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