Frequent reversible membrane damage in peripheral blood B cells in human T cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP)

Abstract

SUMMARY Apoptosis in peripheral blood lymphocyte populations in HTLV-I-infected people in vivo was examined, to study the lymphocyte dynamics in HTLV-I infection. Freshly isolated lymphocytes from 10 non-infected healthy people, eight asymptomatic HTLV-I carriers and 15 patients with HAM/TSP were stained with FITC-labelled annexin V to detect phosphatidylserine (PS) residue exposure at the outer plasma membrane leaflet as an early marker of apoptosis. There was no significant difference in annexin V positivity in CD4+ and CD8+ lymphocytes between non-infected subjects, asymptomatic carriers and HAM/TSP patients, but there was a greatly increased exposure of PS on CD19+ lymphocytes (B cells) detected by FITC–annexin V in 12 out of 15 (80%) HAM/TSP patients, while only two out of eight (25%) asymptomatic carriers and none of the non-infected healthy people showed this aberrant PS exposure on B cells. The intensity of annexin V staining of B cells in HAM/TSP was intermediate, as distinct from the high annexin V staining on advanced apoptotic cells. However, annexin V positivity was decreased when the cells were stained after 24 h of culture, suggesting that the intermediate PS exposure on the B cell in HAM/TSP is not a consequence of an apoptotic process, but rather reflects reversible membrane damage. B cells with PS exposure in vivo might provide a site for coagulation and inflammation, and so contribute to the pathogenesis of HAM/TSP and its complications.