CCR5 Delta 32 Genotype Leads to a Th2 Type Directed Immune Response in ESRD Patients

Background: In patients with end stage renal disease (ESRD) we observed protection from inflammation-associated mortality in CCR5 Delta 32 carriers, leading to CCR5 deficiency, suggesting impact of CCR5 Delta 32 on inflammatory processes. Animal studies have shown that CCR5 deficiency is associated with a more pronounced Th2 type immune response, suggesting that in human CCR5 Delta 32 carriers the immune response may be more Th2 type directed. So, in the present study we determined the Th1-Th2 type directed immune response in ESRD patients carrying and not carrying the CCR5 Delta 32 genetic variant after stimulation.

Methodology/Principal Findings: We tested this hypothesis by determining the levels of IFN-gamma and IL-4 and the distribution of Th1, Th2 and Th17 directed circulating CD4+ and CD8+ T cells and regulatory T cells (Tregs) after stimulation in ESRD patients with (n = 10) and without (n = 9) the CCR5 Delta 32 genotype. The extracellular levels of IFN-gamma and IL-4 did not differ between CCR5 Delta 32 carriers and non carriers. However, based on their intracellular cytokine profile the percentages IL-4 secreting CD4+ and CD8+ T cells carrying the CCR5 Delta 32 genotype were significantly increased (p = 0.02, respectively p = 0.02) compared to non carriers, indicating a more Th2 type directed response. Based on their intracellular cytokine profile the percentages IFN-gamma and IL-17 secreting T cells did not differ between carriers and non-carriers nor did the percentage Tregs, indicating that the Th1, Th17 and T regulatory response was not affected by the CCR5 Delta 32 genotype.

Conclusions/Significance: This first, functional human study shows a more pronounced Th2 type immune response in CCR5 Delta 32 carriers compared to non carriers. These differences may be involved in the previously observed protection from inflammation-associated mortality in ESRD patients carrying CCR5 Delta 32.