Blood Mononuclear Cells in Patients with HTLV-I-Associated Myelopathy: Lymphocytes Are Highly Activated and Adhesion to Endothelial Cells Is Increased

Abstract

We have investigated lymphocyte subpopulations and blood mononuclear cell (MNC) adhesion to activated endothelial monolayers in patients with human T lymphotropic virus type I (HTLV-I) associated myelopathy (HAM), in HTLV-I asymptomatic carriers (carriers), and in seronegative controls. HAM patients and carriers had higher levels of CD4+CD29+ “memory cells” than controls (P < 0.05). The percentage of CD3+CD27− “primed T cell” was elevated in patients with HAM (P < 0.05), but not in carriers. HAM patients had higher levels of CD8+CD57+ “cytotoxic cells” (P < 0.05) than controls and carriers. The percentages of CD4+ cells coexpressing activation markers HLA-DR and CD25, and of CD8+ cells expressing HLA-DR, were significantly higher in HAM patients and carriers than in controls. Functional experiments indicated that MNC from HAM patients adhered more to activated endothelial monolayers than MNC from carriers or controls. Blocking studies demonstrated that the adhesion molecules VLA-4 and ICAM-1 and also L-selectin all contributed to increased binding. Analysis of expression of molecules involved in adhesion indicated that in HAM patients, L-selectin (CD62L) expression on CD4+ and CD8+ subsets was lower than in controls. Interestingly, HAM patients had a lower percentage of CD4+ subsets expressing L-selectin than carriers (P < 0.05). In contrast, the percentage of CD4+ and CD8+ cells expressing VLA-4 (CD49d) was found to be higher in both HAM patients and carriers compared with controls. After 2 days in culture without mitogen, the percentage of T cells expressing ICAM-1 (CD54) increased in culture in carriers and more profoundly in HAM, but not in controls (P < 0.05). After culture, T cells expressing the early activation antigen CD69 were also increased in HAM and carriers (P < 0.05) but not in controls. Interestingly, the levels of CD8+ cells coexpressing activation antigen HLA-DR and CD38 were higher in HAM patients compared with both carriers and controls (P < 0.05) after culture. These findings are consistent with the observations that HTLV-I produces chronic lymphocyte activation with increased adhesion. This may be sufficient to initiate events leading to central nervous system inflammation and ultimately to HAM.