Asthma and gender impact accumulation of T cell subtypes.
BACKGROUND
The "Th2 hypothesis for asthma" asserts that an increased ratio of Th2:Th1 cytokine production plays an important pathogenic role in asthma. Although widely embraced, the hypothesis has been challenged by various empirical observations and has been described as overly simplistic. We sought to establish whether CD3+CD28-mediated and antigen-independent accumulation of type 1 and type 2 T cells differs significantly between nonasthmatic and asthmatic populations.


METHODS
An ex vivo system was used to characterize the regulation of IFN-gamma-producing (type 1) and IL-13-producing (type 2) T cell accumulation in response to CD3+CD28 and IL-2 stimulation by flow cytometry.


RESULTS
IL-13-producing T cells increased in greater numbers in response to antigen-independent stimulation in peripheral blood lymphocytes from female atopic asthmatic subjects compared with male asthmatics and both male and female atopic non-asthmatic subjects. IFN-gamma+ T cells increased in greater numbers in response to either antigen-independent or CD3+CD28-mediated stimulation in peripheral blood lymphocytes from atopic asthmatic subjects compared to non-asthmatic subjects, regardless of gender.


CONCLUSIONS
We demonstrate that T cells from asthmatics are programmed for increased accumulation of both type 2 and type 1 T cells. Gender had a profound effect on the regulation of type 2 T cells, thus providing a mechanism for the higher frequency of adult asthma in females.
Loza
Matthew J
MJ
Department of Internal Medicine, Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. MLoza@ITS.JNJ.COM
Foster
Susan
S
Bleecker
Eugene R
ER
Peters
Stephen P
SP
Penn
Raymond B
RB
D000328:Adult; D001249:Asthma / Q000276:immunology*; D018106:CD28 Antigens / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D011994:Recombinant Proteins / Q000378:metabolism; D012737:Sex Factors; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D018106:CD28 Antigens; D017252:CD3 Complex; C508594:IL2 protein, human; D018793:Interleukin-13; D007376:Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma