The CD4+ T lymphocyte is a site of steroid resistance in asthma.
Phytohaemagglutinin (PHA)-induced T-cell proliferation is suppressed completely in steroid-sensitive asthma (SSA) by fluticasone propionate (FP). By contrast, in patients with steroid-resistant asthma (SRA), this proliferative response is only partially attenuated by steroids, which suggests that the T lymphocyte may harbour a key molecular defect in these patients. Both CD4+ and CD8+ T cells may be involved in orchestrating the inflammation underlying asthma. We examined whether CD4+ or CD8+ T cells isolated from SRA and SSA patients are equally susceptible to steroid suppression of PHA-induced proliferation. Complete suppression of CD4+ T-lymphocyte proliferation was seen in both SSA and control subjects at concentrations of 10(-9) M FP. In contrast, proliferation of CD4+ T cells from SRA patients was only partially inhibited, even at 10(-6) M FP. CD8+ responses from SRA, SSA and controls were all similar, with only a partial suppression of proliferation at 10(-6) M FP. Differential suppression by FP of CD4+ T cells has thus been demonstrated between SRA and SSA patients.
Syed
F
F
Molecular Medicine Unit, University of Leeds, St James's University Hospital, UK. rmrfs@stjames.leeds.ac.uk
Bingham
B
B
Johnson
M
M
Markham
A F
AF
Morrison
J F
JF
D000328:Adult; D000730:Androstadienes / Q000494:pharmacology*; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001249:Asthma / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects; D004306:Dose-Response Relationship, Immunologic; D004351:Drug Resistance / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D000068298:Fluticasone; D006801:Humans; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000276:immunology
D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D010835:Phytohemagglutinins; D000068298:Fluticasone