BACKGROUND:Human tumor necrosis factor-like molecule 1A (hTL1A) is a strong T helper cell type 1 (Th1) co-stimulator.Guillain-Barre syndrome (GBS) is an autoimmune disorder of the nervous system,which is mediated by Th1 cells.OBJECTIVE:To determine hTL1A expression in peripheral blood T lymphocytes of acute GBS children and the effects of hTL1A on secretion of interferon-γ.DESIGN,TIME AND SETTING:A randomized,controlled,neuroimmunological in vitro study was performed at the Central Laboratory of First Hospital of Jilin University,China from November 2005 to November 2007.MATERIALS:Venous blood samples were obtained from 6 healthy donors,aged 6-12 years (all routine blood examination items were normal),and 6 additional children with acute GBS,aged 6-12years.The GBS children fell itl within 1 week and were not treated with hormones or immunoglobulin.Purified recombinant human soluble tumor necrosis factor-like molecule 1A (rhsTL1A,1 mg/mL,relative molecular mass 22 000,6×His tag,soluble form) was supplied by the Central Laboratory of First Hospital of Jilin University,China.METHODS:Peripheral blood mononuclear cells were isolated from healthy donors using the standard Ficoll gradient centrifugation and were incubated in 96-well culture plates.The cells were assigned to the following groups:control (2 μg/mL phytohemagglutinin),2 μg/mL phytohemagglutinin+25,100 and 400 ng/mL rhsTL1A.T cell proliferation was quantified using the tritiated thymidine (~3H-TdR) method.Serum interferon-γ levels in acute GBS children were detected by enzyme-linked immunosorbent assay (ELISA).The ratio of hTL1A-positive T cells to CD3-positive T cells in peripheral blood of acute GBS children was determined using flow cytometry.Following in vitro pre-activation of peripheral blood mononuclear cells by 2 μg/mL phytohemagglutinin,the peripheral blood mononuclear cells were treated with 400 ng/mL exogenous rhsTL1A.Finally,peripheral blood mononuclear cell-secreted interferon-γ levels were measured by ELISA.MAIN OUTCOME MEASURES:The following parameters were measured:rhsTL1A stimulation index to stimulate proliferation of T cells;the serum interferon-γ levels in acute GBS children;the ratio of hTL1A-positive cells to CD3-positive cells;the levels of interferon-γ secreted by peripheral blood mononuclear cells in acute GBS children,as well as rhsTL1A-stimulated interferon-γ levels.RESULTS:T cell proliferation assay revealed that the stimulation index in each rhsTL1A group was greater than the control group.The stimulation index of the 400 ng/mL rhsTL1A group was the greatest.Serum interferon-γ levels in acute GBS children were significantly greater than the control group (P＜0.05).The ratio of hTL1A+ CD3+ T cells to CD3+ T cells in acute GBS children was significantly greater than the control group (P＜0.01).Phytohemagglutinin stimulated peripheral blood mononuclear cells to a greater extent than 400 ng/mL rhsTL1A in the acute GBS group,and the secreted interferon-γ levels were significantly increased (P＜0.05).CONCLUSION:In T cells pre-activated with 2 μg/mL phytohemagglutinin,proliferation was effectively increased with 400 ng/mL rhsTL1A treatment.Expression of hTL1A was increased in activated T cells from peripheral blood of acute GBS children,followed by increased interferon-γ secretion.These mechanisms are considered to be part of the pathological process that induces the secretion of inflammatory cytokines in GBS syndrome.