Presentation: Evaluation of Gender Differences in T Cell Gene Expression by cDNA Microarray Analysis (2007)

141 Evaluation of Gender Differences in T Cell Gene Expression by cDNA Microarray Analysis

BACKGROUND: Many autoimmune diseases are more prevalent in women than in men. T lymphocytes play a crucial role in the pathogenesis of many autoimmune diseases such as systemic lupus erythematosis, multiple sclerosis and rheumatoid arthritis. Sexual dimorphism in gene expression may play a critical role in clinical outcome.
PURPOSE: To determine gender differences in T cell gene expression.
METHODS: T cells were isolated from 3 men and 3 women, stimulated with PHA cultured 3 days, then restimulated or not for 6 hours with PMA + ionomycin. Total RNA isolation and DNA microarray analyses were done using standard protocols. Gene sets with differential expression between women and men were analyzed using Genomatix BiblioSphere software to identify overrepresented Gene Ontology (GO) groups. For genes identified by this approach, promoters were extracted from genomic sequences. Transcription factor binding site analysis combined with literature search was performed using Genomatix MatInspector and BiblioSphere.
RESULTS: 305 genes were differentially expressed in unrestimulated T cells from men and women. 25% (77) of the 305 genes were more highly expressed in women than in men, and the genes included sustained interferon gamma (IFN-γ) expression in women. Upon restimulation of the cells with PMA + ionomycin, 1846 genes were differentially expressed between men and women. Of these genes, 71% (1318) were expressed higher in women. When the GO-Filter “biological process” was applied to these 1318 genes, immune response genes were significantly over-represented. In contrast, immune response genes were not enriched in the genes expressed more highly in men. Among the immune response genes differentially expressed in women (139 total); inflammation-associated genes (43) and “immune response regulation” genes (19) represented a significant proportion. In addition to IFN-γ, lymphotoxin beta (LTB), granzyme A (GZMA), and granulysin (GNLY) were the most highly expressed in women compared to men. Estrogen response elements were identified in the promoters of 48 of the 139 differentially expressed genes identified as over-expressed in women.
CONCLUSIONS: More inflammatory immune genes are expressed and at higher levels in T cells from women than from men. These data suggest that women are more prone to inflammatory T cell responses under conditions of repeated stimulation. This hyper-reactivity may contribute to gender difference observed in chronic immune stimulation as seen in autoimmune diseases.

 A. Hewagama, None; D.R. Patel, None; F.M. Strickland, None; B. Richardson, None.