Clonal expansion of T cells infiltrating in the airways of non-atopic asthmatics.
CD4+ T cells are thought to play an important role in airway inflammation in both atopic and non-atopic asthma. However, the mechanism by which T cells are activated in non-atopic asthma, where there is no causative antigen identified, is unknown. To elucidate this issue, we analysed T cell receptor (TCR) Vbeta gene clonotypes of T cells in the bronchoalveolar lavage fluids (BALF) of non-atopic asthmatics using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis and a sequencing method. We found that the numbers of TCR Vbeta gene clonotypes of T cells in the BALF of non-atopic asthmatics were significantly increased compared with those of peripheral blood lymphocytes (PBL). We also found that there were several shared amino acid motifs in complementarity-determining region 3 (CDR3) of TCR Vbeta genes from those T cell clones in BALF of non-atopic asthmatics, whereas these shared motifs were not found in the same Vbeta family genes from PBL in the patients. Moreover, a conserved amino acid sequence was detected in two patients who shared a common HLA-DR allele. These results indicate that the infiltrating T cells in the airways of non-atopic asthmatics recognize relatively limited epitopes of antigens and are clonally expanded by antigen-driven stimulation.
Umibe
T
T
Department of Internal Medicine II, Chiba University School of Medicine, Japan.
Kita
Y
Y
Nakao
A
A
Nakajima
H
H
Fukuda
T
T
Yoshida
S
S
Sakamaki
T
T
Saito
Y
Y
Iwamoto
I
I
D000328:Adult; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D002454:Cell Differentiation; D002465:Cell Movement / Q000276:immunology*; D005260:Female; D005803:Genes, Immunoglobulin; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D012137:Respiratory System / Q000276:immunology* / Q000473:pathology*
D007135:Immunoglobulin Variable Region; D016693:Receptors, Antigen, T-Cell, alpha-beta