Human allergies are an overreaction of the immune system and are studied in the Contact Hypersensitivity Assay (CHS), which serves as a faithful model of the human condition. In the immune system the Stat5 transcription factors are essential both for lymphocytes development and acute immune responses.
Researchers from the LBI-CR with others investigated now the role of Stat5 gene dosage in contact allergies through the effect of Stat5 gene dosage modulation on CHS in mice. Transgenic animals heterozygous for the germline Stat5 null allele were subjected to CHS assay. To dissect cell type sensitive to Stat5 gene dosage, one Stat5 allele was removed by Lck-Cre- mediated deletion (Stat5(ΔT/+). Frequency of T -, B- cells and monocytes were analyzed in Stat5(ΔT/+) and wild type animals by flow cytometry. Proliferation of Stat5(ΔT/+) CD8(+) T cells were studied in vitro by stimulation with IL-4 and IL-2 cytokines and changes in expression of Stat5 target genes were assayed by quantitative real time PCR assay.
Haplo-insufficiency of Stat5 in T cells leads to reduction of CD8(+) T cells in all lymphoid organs and attenuates CHS response. Stat5(ΔT/+) CD8(+) T cells failed to fully activate Stat5 dependent expression of cell cycle/survival target genes, such as bcl-2 and pim1, and to proliferate efficiently in response to IL-2 and IL-4 cytokine. The researchers therefore concluded that Stat5 as a dose dependent regulator of CD8(+) T cell functions in contact allergies and suggest that modulation of Stat5 dosage could be used to target contact allergies in humans.
The report "Stat5 gene dosage in T cells modulates CD8+ T cell homeostasis and attenuates contact hypersensitivity response in mice" by H. Nivarthi et al was published in Allergy.