Evaluation of CD4(+)CD25(+)FoxP3(+) T cell populations, IL-10 production, and their correlation with clinical and biochemical parameters in sickle cell anemia patients with leg ulcers

Abstract

Leg ulcers (LUs) are a debilitating complication of sickle cell anemia (SCA), with inflammation known to play a crucial role in their pathogenesis. Many studies have described the roles of T helper type 1 (Th1) and Th2 pathways in SCA; however, defects in anti-inflammatory responses are poorly understood. We evaluated interleukin (IL)-10 levels in serum and peripheral blood mononuclear cells (PBMCs) in SCA patients with leg ulcers (SCALU) and without leg ulcers (SCAWH) in addition to CD4(+) CD25(+)FoxP3(+) T cell populations and their its IL-10 expression. In stimulated and unstimulated PBMC cultures, SCALU patients produced higher levels of IL-10 than those in the SCAWH group. Higher levels of IL-10 in SCALU patients correlated with a history of osteonecrosis in stimulated and unstimulated cultures when compared with those in SCAWH. Immunophenotyping revealed that SCALU patients had a higher proportion of CD4(+)CD25(+)FoxP3(+), Tr1 and CD4(+)CD25(+)FoxP3(+)IL-10(+) T cells than other groups. Our findings revealed that IL-10 levels were increased in unstimulated cells from the SCALU group, and that this group also presented with a predominant CD4(+) CD25(+)FoxP3(+) cell population despite many of those cells being IL-10 negative.

Keywords: Immunophenotyping; Inflammation; Interleukin 10; Leg ulcer; Sickle cell anemia; T regulatory cells.