T Lymphocyte Subsets and Binding of T lymphocyte to Human Dermal Microvascular Endothelial Cells in Behcet's Disease

Kim, Hee Sung; Bang, Dong Sik; Lee, Kwang Hoon

Abstract

BACKGROUND: Behcets disease represents a polysymptomatic, recurrent vasculitis' with a chronic course. Its etiology and pathogenesis still remains unclear. Several immunological abnormalities have been described in this disease and altered cell mediated immunity especially has been suggested to play an important role in the pathogenesis. Recently, suppressor-inducer (naive, CD4-CD45RA+ ) and helper-inducer (memory, CD4-CD45RO+) human T cell subsets have been identified by their relevant monoclonal antibodies. It has heen suspected that human dermal microvascular endothelial cells(HDMEC) are an important part in the pathogenesis of Behcets disease. However, there was no report for HDMEC-T lymphocyte adhesion in Behcets disease,
OBJECTIVE
We have investigated the subpopulation differences in CD4- T lymphocytes and the adhesiveness of T lymphocytes to cultured HDMEC in the presence of IL-1 alpha, or TNF-alpha using T lymphocytes isolated from normal human subjects and Behcets disease patients respectively.
METHODS
T lymphocyte subsets were evaluated by the two-color immuno-fluorescence flow cytometric analysis using anti CD4-, CD8-, CD45RA- and CD45RO monoclonal antibodies. The binding assay of T lymphocytes to HDMEC was performed before and after stimulating HDMEC with IL-l alpha or TNF-alpha.
RESULTS
1. The number of CD4- T cells and the CD4+ to CD8+ ratio decreased in patients with Behcets disease compared to normal controls. 2. In the CD4+ T cell subpopulation, there was a significant decrease in the CD4+CD45RA+cell number with a slight increase in the CD4+ CD45RO+ cell number. 3. After stimulating HDMEC with IL-la and TNF-a, the degree of T lymphocyte-HDMEC adhesion generally increased in an E:T ratio dependent, manner in patients with Behcets disease compared to normal controls. 4. Increased binding of CD4+ CD45RA+ naive T lymphocytes and CD4+CD45RO+ memory T lymphocytes to HDMEC was induced after stimulation with IL-1 alpha and TNF-alpha in both patients and normal controls. The increasing rate was higher in Behcets disease patients than in normal controls. There was no difference in T lymphocyte-HDMEC adhesion between memory and naive T lymphocytes.
CONCLUSION
From these findings it can be postulated that the decrease in the CD4+CD45RA+ count may lead to the inactivation of CD8 suppressor cells resulting in abnormal immune suppression shown in Behcets disease. Proinflammatory cytokines may also play an integral role in the pathogenesis of Behcet's disease by activating endothelial cells increasing the interaction between T lymphocytes and endothelial cells. Increasing the interaction between T lymphocytes and HDMEC may be indirect evidence of activation of cell-mediated immunity.