Altered expression of Th1-type chemokine receptor CXCR3 on CD4+ T cells in myasthenia gravis patients.

The expression of chemokine receptors on peripheral blood lymphocytes and thymocytes of myasthenia gravis (MG) patients was analyzed before and after therapy with special reference to the thymic histopathology. Before therapy, MG patients showed reduced frequency of CD4+ T cells expressing T-helper1 (Th1) type chemokine receptor CXCR3, with a significantly lower frequency in the thymoma group than in the thymic hyperplasia group, while the frequencies of CXCR3-positive CD8+ T cells remained normal irrespective of the thymic pathology. Both CD4+ cells and CD8+ cells of the hyperplasia group showed significantly increased expression of CCR1 on the cells followed by a reduction to the control level after therapy. No significant changes in the frequencies of CCR2, CCR3, CCR4, and CCR5 were observed in either MG group. There was a significant inverse correlation between the percentage of CXCR3-positive CD4+ T cells and the disease severity assessed with the MGFA scale (Fig. 1, r=-0.55, p=0.0047). The CXCR3 expression on CD4+ cells was increased toward the control level long after the initiation of therapy. The thymomas showed significantly higher percentages of CXCR3-positive CD4+CD8- single positive cells than the control thymuses and, though not significantly, the hyperplastic thymuses also showed higher percentages. These results indicated that Th1-type chemokine signalings were altered in the MG patients, particularly those with thymoma, and that the thymus and thymoma are important sites of Th1-type reactions. The slow clinical improvement of MG symptoms after treatment may be explained partly by the gradual normalization of CXCR3-mediated signaling.