CD4+ CD30+ T cells perpetuate IL-5 production in Dermatophagoides pteronyssinus allergic patients.
BACKGROUND
Airway allergic diseases are regulated by interleukin (IL)-5, which causes infiltration of eosinophils into the bronchial epithelium, and by IL-4 which increases serum immunoglobulin E (IgE) production and promotes CD30 expression on Th cells. CD30 generates a costimulatory signal involved in apoptosis or cell proliferation, depending on the microenvironment. Our aims were: (i) to analyze if CD4+ CD30+ T cells from allergic patients proliferate in response to Dermatophagoides pteronyssinus, and (ii) if upon stimulation this cell population produces IL-4 and IL-5.


METHODS
Peripheral blood mononuclear cell (PBMC) from 17 allergic rhinitis and mild allergic asthma patients and 12 healthy nonallergic individuals were stimulated with allergen in the presence or absence of anti-IL-4, anti-IL-5 or anti-IL-4Ralpha monoclonal antibodies (mAbs). TdT-mediated dUTP nick end-labeling (TUNEL) assay, 7-aminoactinomycin-D (7-AAD) intercalation, and flow cytometry were used to determine the CD4+ CD30+ blasts percentage, cell proliferation, apoptosis, and intracellular cytokines after 7 culture days.


RESULTS
Cell proliferation induced with allergen showed that 90% of the allergen-stimulated blasts were CD4+, 50% of which were CD30+. Allergen-stimulated PBMC showed a progressive increase (mean: from 7% to 23%) of CD4+ CD30+IFN-gamma+ and CD4+ CD30+IL-4+ blasts which diminished (mean: 6%) after 5 culture days. In contrast, CD4+ CD30+IL-5+ blasts showed a continuous progression (from 12% to 24%) that maintained after 7 culture days. The vast majority of CD4+ CD30+ blasts were negative to 7-AAD or TUNEL. Additionally, a significant decrease (34%) was observed in the number of CD4+ CD30+ blasts when IL-4 was neutralized.


CONCLUSIONS
These data suggest that specific allergen stimulation of PBMC isolated from allergic patients generates a nonapoptotic CD4+ CD30+ blast subset that produces IL-5.
Garfias
Y
Y
Instituto de Oftalmología, Fundación Conde de Valenciana, Mexico.
Ortiz
B
B
Hernández
J
J
Magaña
D
D
Becerril-Angeles
M
M
Zenteno
E
E
Lascurain
R
R
D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000494:pharmacology*; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology; D001249:Asthma / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D040002:Dermatophagoides pteronyssinus; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015848:Interleukin-5 / Q000096:biosynthesis*; D017730:Ki-1 Antigen / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D011336:Probability; D006255:Rhinitis, Allergic, Seasonal / Q000097:blood; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric
D000485:Allergens; D039741:Antigens, Dermatophagoides; D015848:Interleukin-5; D017730:Ki-1 Antigen