CHARACTERIZATION OF CD4(-HELPER CELLS IN PATIENTS WITH KAWASAKI-DISEASE (KD) - PREFERENTIAL PRODUCTION OF TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) BY V-BETA-2(-) OR V-BETA-8(-) CD4(+) T-HELPER CELLS() T)

KD is an acute febrile illness in children characterized by coronary a rteritis accompanied by aneurysm and thrombotic occlusion. The etiolog y of KD is unknown. It has been recently reported that KD is associate d with the selective expansion of V beta(2+) and V beta 8.1(+) T cells in peripheral blood lymphocytes (PBL), by studying the T cell recepto r (TCR) repertoire of in vitro activated T cells. KD may therefore be caused by a superantigen [1-3]. To understand better the immunopatholo gy of KD, we investigated TCR V beta 2 and V beta 8.1 expression on bo th the T cells of freshly isolated PBL and T cell clones (TCC) from pa tients with KD. Cytokine production by TCC was also studied. Blood sam ples were obtained from patients with acute (n = 20) and convalescent (n = 20) KD, age-matched 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 V beta 2(+) or V beta 8.1(+) T cells of freshly isolated PBL. The same was true for th e CD4(+) or CD8(+) T cell subsets. One hundred and five TCC (98 CD3(+) CD4(+) CD8(-) and seven CD3(+) CD4(-) CD8(+)) established from the af fected skin, lymph node or PBL of six patients with KD were also negat ive for either V beta 2 or V beta 8.1 TCR. Sixty-eight of 105 TCC (65% ) produced detectable levels (>5 pg/ml) of TNF-alpha (6-1016 pg/ml), i n 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, respecti vely, in the absence of any stimuli. Stimulation with phytohaemaggluti nin (PHA) and phorbol myristate acetate (PMA) induced most TCC to prod uce higher amounts of TNF-alpha, IL-2 and IL-6. These results suggest that CD4(+) T helper cells expressing TCR-beta other than V beta 2 or V beta 8 receptor, primarily through TNF-alpha production, are involve d in the immunopathology of KD.