Defective Tregs expression of the NTPDase CD39 in lupus (89.24)

Abstract

Abstract The role of aberrations in the regulatory T cells (Tregs) pool for the development of systemic lupus erythamatosus (lupus) remains uncertain. Treg-mediated generation of adenosine, dependent on the ectonucleotidase CD39, is an important mechanism for suppression of T-cell responses. We studied 15 SLE patients along with 6 rheumatoid arthritis and 24 healthy controls. Levels of Treg phenotypic markers, including CD39 expression, were studied by flow cytometric analysis. Varying numbers of sorted Tregs cells were co-cultured with responder T (Tresp) cells, with proliferation assessed by 3H-thymidine incorporation. The proportion of Foxp3+ CD25+high CD127-/low Tregs was similar between lupus and control populations. CD39-expressing Tregs comprised 37 ± 13% of the Treg population in healthy controls and 36 ± 21% in lupus subjects using nonsteroidal immunosuppressants to control active disease, but was nearly absent in 5 of 6 lupus subjects with minimally active disease. In lupus subjects with the CD39 defect, Treg-mediated suppression was significantly reduced and, unlike in healthy control subjects, adenosine receptor antagonism could not reverse the observed suppression. These results suggest that functional defects in Tregs, rather than reduced Treg numbers, may be important for the loss of peripheral tolerance in lupus. Supported by NIH RO1-AR39501,WFUSM Venture Funds.