Expression of OX40 (CD134) on CD4+ T-cells from patients with myasthenia gravis

Abstract

Myasthenia gravis (MG) is commonly regarded as the prototype of an antibody-mediated, organ-specific autoimmune disease. Antibodies against the acetylcholine receptor (AChR) on the muscle endplate trigger its typical clinical manifestations of weakness and fatiguability. T-B cell interactions are thought to play a crucial role in the pathogenesis of MG. OX40 (CD134), a costimulatory molecule that is expressed on activated CD4+ T-cells, might contribute to the development or pathogenesis of immune-mediated diseases such as rheumatoid arthritis and graft-versus-host disease. In the present study, we investigated the expression of OX40 on CD4+ T-cells from patients with MG and healthy individuals. Results from 36 MG patients and 28 healthy controls revealed that more freshly isolated CD4+ T-cells from MG patients expressed OX40 than cells from healthy individuals. High levels of antibodies against the AChR, thymic hyperplasia and onset at an early age were associated with elevated expression of OX40. Upon activation by various concentrations of anti-CD3 antibodies, CD4+ T-cells from MG patients showed a tendency toward higher levels of OX40 expression than cells from healthy individuals. Given the role of OX40 in the immune system, we conclude that OX40 might contribute to the development of MG.

Fig. 1

OX40+ expression on freshly isolated CD4+ T-cells from MG patients (n = 36) and healthy controls (HC) (n = 28) (P = 0·012). The vertical lines indicates the median levels of CD4+ T-cells expressing OX40.

Fig. 2

Representative examples of flow cytometry plots showing (a) CD4+OX40+ T-cells from one MG patient (15·5% of total CD4+T-cells expressed OX40) and surface expression of (b) CD28 (100%) (c) CD152 (CTLA-4) (< 1%) (d) CD25 on CD4+OX40+ T-cells. CD4+OX40+ T-cells exhibited elevated CD25 (91%) expression compared with CD4+OX40- T-cells (54·5%).

Fig. 3

(a) Induction of OX40 expression on CD4+ T-cells after 24 h (a). PBMC from MG (•, n = 5) and HC (▪, n = 5) were stimulated in parallel with immobilized anti-CD3 antibody at the indicated coating concentrations for 24 hRepresentative examples of flow cytometry plots showing (b) CD4+OX40+ T-cells from one MG patient stimulated with anti-CD3 antibody for 24 h and surface expression of (c) CD69 (89%) (d) CD152 (CTLA-4) (18%) on CD4+OX40+ T-cells.