Increase of both circulating Th1 and Th2 T lymphocyte subsets in IgA nephropathy

Abstract

SUMMARY IgA nephropathy (IgAN), characterized by glomerular deposition of IgA and frequently elevated plasma IgA levels, has increased T helper cell activity. In vitro measurement of cytokines in supernatant of cultured peripheral lymphocytes revealed conflicting findings. We examined the profile of cytokine mRNA expressed in purified CD4+ cells in patients with IgAN in order to study their pattern of Th1 (releases IL-2 and interferon-gamma (IFN-γ)) and Th2 (releases IL-4 and IL-5) T cell response. We assessed the circulating CD4+ T cells in patients and normal controls by the expression of messenger RNA (mRNA) for IL-2, IL-4, IL-5 and IFN-γ. The cytokine mRNAs were analysed with reverse transcription-polymerase chain reaction and were measured semiquantitatively by using a housekeeping gene, β-actin. Compared with the control subjects, CD4+ T lymphocytes from patients with IgAN expressed a higher level of IL-2 mRNA (P=0·007), IFN-γ mRNA (P = 0·04), IL-4 mRNA (P = 0·048), and IL-5 mRNA (P=0·016). Within these patients with IgAN, a good correlation was demonstrated between the gene expression of cytokines in Th1 or Th2 cells. The IL-2 mRNA levels in Th1 cells from these patients with IgAN also correlated significantly with the IL-4 or IL-5 mRNA levels in their Th2 cells. Our study revealed IgAN is associated with activation in circulating lymphocytes of the IL-2, IFN-γ, IL-4 and IL-5 gene cluster, a pattern compatible with activation of both the Th1- and Th2-like T lymphocyte population. The increased transcription of these cytokine genes may be contributory to the immunopathologic findings in IgAN.