Characterization of CD4+ T helper cells in patients with Kawasaki disease (KD): preferential production of tumour necrosis factor-alpha (TNF-α) by Vβ2− or Vβ8− CD4+ T helper cells

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Abstract
SUMMARY: KD is an acute febrile illness in children characterized by coronary arteritis accompanied by aneurysm and thrombotic occlusion. The etiology of KD is unknown. It has been recently reported that KD is associated with the selective expansion of Vβ2+ and Vβ8.1+ T cells in peripheral blood lymphocytes (PBL), by studying the T cell receptor (TCR) repertoire of in vitro activated T cells. KD may therefore be caused by a superantigen [1–3]. To understand better the immunopathology of KD, we investigated TCR Vβ2 and Vβ8.1 expression on both the T cells of freshly isolated PBL and T cell clones (TCC) from patients with KD. Cytokine production by TCC was also studied. Blood samples were obtained from patients with acute (n= 20) and convalescent (n= 20) KD, agematched children with non-infectious diseases (n= 18), and healthy adults (n= 20). Among these four groups, there were no significant differences in the percentages of either Vβ2+ or Vβ8.1+. T cells of freshly isolated PBL. The same was true for the CD4+ or CD8+ T cell subsets. One hundred and five TCC (98 CD3+ CD4+ CD8− and seven CD3+ CDA− CD8+) established from the affected skin, lymph node or PBL of six patients with KD were also negative for either Vβ2 or Vβ8.1 TCR. Sixty-eight of 105 TCC (65%) produced detectable levels (>5 pg/ml) of TNF-α (6–1016 pg/ml), in the absence of any stimuli. In contrast, only 11 (10%) of 105 TCC or 7(7%) of 97 TCC produced detectable levels of IL-2 or IL-6, respectively, in the absence of any stimuli. Stimulation with phytohaemagglutinin (PHA) and phorbol myristate acetate (PMA) induced most TCC to produce higher amounts of TNF-α, IL-2 and IL-6. These results suggest that CD4+ T helper cells expressing TCR-β other than Vβ2 or Vβ8 receptor, primarily through TNF-α production, are involved in the immunopathology of KD.