Mechanism of T cell activation in the airways of asthma

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Asthma is characterized by airway inflammation with prominent infiltrates of eosinophils and CD4 T cells. However, the mechanism by which T cells of nonatopic asthmatics are activated is unknown. To determine whether T cells are clonally activated by an unidentified antigen in nonatopic asthma, we analyzed T cell receptor (TCR) Vbeta genes of T cells in bronchoalveolar lavage fluids (BALF) of nonatopic asthmatics by using RT-PCR and subsequent single-strand conformation polymorphism (SSCP) analysis. PCR-SSCP analysis showed that several clonotypic bands in smears were found in most of Vbeta genes from BALF and PBL of nonatopic asthma patients. The numbers of the bands encoding each Vbeta gene from BALF significantly increased as compared with those from PBL in four of seven subjects (P<0.05). In addition, the numbers of T cell clones expressing TCR Vbeta6, Vbeta12, and Vbeta17 genes in BALF significantly increased in comparison to those in PBL (p<0.05). Moreover, sequencing analysis of CDR3 region of TCR Vbeta genes from BALF-accumulated T cell clones showed that several increased amino acid motifs were found in six subjects analyzed at a frequency of approximately 8-9% of sequenced clones, which were specifically found in each individual patient. Interestingly, two clones sharing an identical motif PF in CDR3 region with different Jbeta gene usage were detected in one patient. Moreover, one conserved amino acid sequence PTGTAG was detected in two patients who shared a common HLA-DR allele. These results suggest that infiltrating T cells in the airways of nonatopic asthmatics might recognize relatively limited epitopes of antigens in the airways and expand by the antigendriven stimulation.