Increased T-cell receptor vbeta8+ T cells in bronchoalveolar lavage fluid of subjects with poorly controlled asthma: a potential role for microbial superantigens.
BACKGROUND
T cells are thought to play an important role in the pathogenesis of chronic asthma. The immunologic triggers that contribute to poorly controlled asthma are unknown but may include infectious agents. Superantigens (SAgs), which stimulate T cells expressing selected T-cell receptor (TCR) beta-chain variable (Vbeta) regions, are known to be an important mechanism by which microbes can contribute to T-cell activation and disease pathogenesis.


OBJECTIVE
We sought to determine the potential role of SAgs in T-cell activation of patients with poorly controlled asthma.


METHODS
We studied the TCR-Vbeta repertoire of bronchoalveolar lavage (BAL) cells and PBMCs from 9 subjects with poorly controlled asthma (FEV1 <75%), 7 subjects with well-controlled asthma (FEV1 >80%), and 8 normal control subjects with the use of anti-TCR-Vbeta-specific mAbs and flow cytometry.


RESULTS
Subjects with poorly controlled asthma had a significantly higher expression of Vbeta8(+) T cells in BAL fluid than subjects with well-controlled asthma and normal control subjects (P <.01) and autologous PBMCs (P <.05). Increased Vbeta8(+) BAL T cells were present in CD4(+) (P <.01) and CD8(+) (P <.05) subsets, suggesting activation by SAgs.


CONCLUSIONS
These results indicate that SAgs are a potential trigger of T-cell activation in poorly controlled asthma.
Divisions of Allergy-Immunology, National Jewish Medical and Research Center, Denver, CO, USA.
P J
PJ
Hauk
S E
SE
Wenzel
A E
AE
Trumble
S J
SJ
Szefler
D Y
DY
Leung
D000328:Adult; D001249:Asthma / Q000276:immunology* / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry*; D005260:Female; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D018089:Superantigens / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000737:chemistry
D007135:Immunoglobulin Variable Region; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens