Haplotype 4 of the multiple sclerosis-associated interleukin-7 receptor alpha gene influences the frequency of recent thymic emigrants

The receptor for the homeostatic T cell cytokine interleukin-7 (IL-7R alpha) has recently shown genetic association to multiple sclerosis (MS). To investigate the functional contribution of IL-7R alpha polymorphisms to the pathogenesis of MS, we correlated the IL-7R alpha haplotypes with different T cell parameters in a group of MS patients and healthy controls. We show that carriers of one of the four IL-7R alpha haplotypes (Hap4) show a higher expression of IL-7R alpha (CD127) on their CD4(+) T cells, compared with noncarriers (P = 0.04). Moreover, Hap4 carriers possess higher frequencies of recent thymic emigrants (RTEs, CD31(+)) in both the regulatory T cell (Treg; P = 0.007) and conventional T cell (Tconv) population (P = 0.0001). This effect is most pronounced within the MS population (Treg, P = 0.0077; Tconv, P = 0.0007), whereas in healthy controls significance was only reached for Tconv (P = 0.043; Treg, P = 0.11). Because previous studies showed a decreased RTE-Treg frequency in MS patients compared to healthy subjects, we here conclude that this decrease is localized within the MS population of non-Hap4 carriers. In conclusion, our findings suggest that IL-7Ra polymorphisms can influence T cell development and homeostasis, and thereby contribute to the altered immune regulation associated with disease development in patients with MS. Genes and Immunity (2010) 11, 326-333; doi:10.1038/gene.2009.106; published online 14 January 2010