Autoimmune neurologic diseases
The interleukin-2 (IL-2) receptor α (CD25) is important for T cell functions. Single nucleotide polymorphisms (SNPs) rs2104286 and rs11256593 in or near the IL2RA gene, that encodes CD25, increase the risk of multiple sclerosis (MS), an immune-mediated disease causing neurological dysfunction and disability. However, the mechanism is poorly understood.
We investigated how MS-associated IL2RA SNPs affected CD25 expression on T cells ex vivo by multiparameter flow cytometry in genotype-selected healthy controls (HC).
The HCs were homozygous carriers for either the risk or protective alleles of IL2RA SNPs rs2104286 and rs11256593. Risk allele carriers were paired with protective allele carriers regarding sex and age and pairs were sampled and analyzed jointly.
We observed that risk allele carriers had a higher frequency of CD25+ recent thymic emigrant CD4+ T cells (p = 0.006) and a lower frequency of CD25+ TFH1 cells (p = 0.001) compared to protective allele carriers. Also, we found that risk allele carriers had lower surface expression of CD25 on post-thymic expanded CD4+ T cells (CD31-CD45RA+) (p = 0.01), CD39+ TReg cells (p = 0.02) and on several CD4+ non-follicular memory subsets. In CD8+ T cells, we found no association between CD25 expression and MS-associated IL2RA SNPs.
In summary, we found novel effects of MS-associated IL2RA SNPs on expression of CD25 on CD4+ T cells. Expression of CD25 is central for T cell responsiveness to IL-2. Thus, risk allele carriers may have differential IL-2 responsiveness that contribute to the immunological alterations in CD4+ T cells observed in MS patients.