Serine leucocyte proteinase inhibitor-treated monocyte inhibits human CD4+ lymphocyte proliferation

Abstract

Summary Serine leucocyte proteinase inhibitor (SLPI) is the main serine proteinase inhibitor produced by epithelial cells and has been shown to be a pleiotropic molecule with anti‐inflammatory and microbicidal activities. However, the role of SLPI on the adaptive immune response is not well established. Therefore, we evaluated the effect of SLPI on lymphocyte proliferation and cytokine production. Human peripheral blood mononuclear cells (PBMC) were treated with mitogens plus SLPI and proliferation was assessed by [3H]thymidine uptake. The SLPI decreased the lymphocyte proliferation induced by interleukin‐2 (IL‐2) or OKT3 monoclonal antibodies in a dose‐dependent manner. Inhibition was not observed when depleting monocytes from the PBMC and it was restored by adding monocytes and SLPI. SLPI‐treated monocyte slightly decreased MHC II and increased CD18 expression, and secreted greater amounts of IL‐4, IL‐6 and IL‐10 in the cell culture supernatants. SLPI‐treated monocyte culture supernatant inhibited the CD4+ lymphocyte proliferation but did not affect the proliferation of CD8+ cells. Moreover, IL‐2 increased T‐bet expression and the presence of SLPI significantly decreased it. Finally, SLPI‐treated monocyte culture supernatant dramatically decreased interferon‐γ but increased IL‐4, IL‐6 and IL‐10 in the presence of IL‐2‐treated T cells. Our results demonstrate that SLPI target monocytes, which in turn inhibit CD4 lymphocyte proliferation and T helper type 1 cytokine secretion. Overall, these results suggest that SLPI is an alarm protein that modulates not only the innate immune response but also the adaptive immune response.

Secretory leukocyte protease inhibitor: A pivotal mediator of anti-inflammatory responses in acetaminophen-induced acute liver failure

“…Although the early increase in circulating levels of SLPI is likely to initially reflect a homeostatic response to the acute liver injury, we detect persistently elevated SLPI levels AALF patients up to 3 days following admission, which are associated with an increased frequency of infection. These findings are of relevance given reports showing that elevated SLPI levels were detrimental in patients suffering from systemic sepsis where it inhibits proinflammatory responses and impairs monocyte driven T‐cell proliferation and T‐helper cell (Th)1 responses . The utility of SLPI as a biomarker of infection and disease severity requires investigation in larger groups of patients suffering from ALF of acetaminophen and nonacetaminophen etiology.…”

“…These findings are of relevance given reports showing that elevated SLPI levels were detrimental in patients suffering from systemic sepsis [12][13][14] where it inhibits proinflammatory responses and impairs monocyte driven T-cell proliferation and T-helper cell (Th)1 responses. 28 The utility of SLPI as a biomarker of infection and disease severity requires investigation in larger groups of patients suffering from ALF of acetaminophen and nonacetaminophen etiology.…”

Intracellular Secretory Leukoprotease Inhibitor Modulates Inositol 1,4,5-Triphosphate Generation and Exerts an Anti-Inflammatory Effect on Neutrophils of Individuals with Cystic Fibrosis and Chronic Obstructive Pulmonary Disease

“…SLPI has been previously reported to exert an anti-inflammatory effect on immune cell function [20, 29], and in this respect SLPI has been shown to inhibit monocytic CD4 lymphocyte proliferation and Th1 cytokine (INF- γ ) release [30]. Indeed, T lymphocytes play a key role in the pathogenesis of CF [31] and COPD [32] lung disease and have been identified as the predominant cell type in subepithelial bronchial tissue of CF patients [31].…”

Immunological Adaptations to Pregnancy in Women with Type 1 Diabetes

“…We found increased expression of MHC-II and decreased expression of CD62L on intermediate monocytes in diabetic pregnant women, suggesting activation of these cells. Decreased MHC-II expression on monocytes is associated with inadequate presentation of antigens to T-cells and disturbed T-cell stimulation 36 . Thus, the ability of these monocytes to present antigens to T-cells is increased in pregnant women with diabetes, which could lead to enhanced activation of the systemic immune response.…”