Chronic Brucellosis Patients Retain Low Frequency of CD4+ T-Lymphocytes Expressing CD25 and CD28 afterEscherichia coliLPS Stimulation of PHA-Cultured PBMCs

Abstract

Chronic brucellosis patients display a defective Th1 response to PHA. We have previously shown that heat-killed B. abortus (HKBA) can downregulate the PHA-induced increase of CD4+/CD25+ and CD14+/CD80+ cells of brucellosis patients. In the present study, we investigate the effect of E. coli LPS, as a potent stimulant of monocytes and autologous T-lymphocytes, on the PHA-cultured PBMCs of the same groups of patients. Thirteen acute brucellosis (AB) patients, 22 chronic brucellosis (CB) patients, 11 “cured” subjects, and 15 healthy volunteers were studied. The percentage of CD4+/CD25+ and CD4+/CD28+ T-lymphocytes as well as CD14+/CD80+ monocytes were analyzed by flow cytometry after PBMCs culture with PHA plus E. coli LPS. A significant decrease in the percentage of CD4+/CD25+ and CD4+/CD28+ T-lymphocytes was observed in CB compared to AB. In HKBA cultures, compared to E. coli LPS-cultures, there was a significant reduction of CD4+/CD25+ T-lymphocytes in all groups and CD14+/CD80+ in patients groups. We suggest that Brucella can modulate host immune response, leading to T-cell anergy and chronic infection.

Mystery of Immune Response in Relapsed Brucellosis: Immunophenotyping and Multiple Cytokine Analysis

“…avoid or manipulate host immunity for their own benefit, and according to our findings, in the case of relapse, there is a decrease in the frequency of both CD4 + T cells and activated T cells (CD3 + HLA-DR + ) in the peripheral blood. Chronic brucellosis patients display a defective Th1 response and a decreased percentage of CD4 + T cells expressing CD25 [22,23] . We hypothesize that the suppression of naïve or activated T cells or a defective Th1 response are either a function of regulatory T (Treg) cells or suppressor T cells, which leads to the progression of infection both in relapse and chronic brucellosis patients.…”

“…Pasquali et al [24] observed that Treg cells suppress the effector functions of CD4 + T cells in infected mice, and they showed that Treg cells allow the expansion of brucellosis. In a clinical investigation, Skendros et al [23] observed that chronic brucellosis patients retain low percentages of CD4 + CD25 + and CD4 + CD28 + T lymphocytes after potent stimulation with phytohemagglutinin-cultured peripheral blood cells using Escherichia coli lipopolysaccharide (LPS). Accordingly, they concluded that Brucella spp.…”

“…One is related to the expansion of Treg cells, and the second is Brucella-acquired cellular anergy. Accordingly, Pasquali et al [23] observed that CD4 + CD25 + Treg cells were responsible for the maintenance and progression of B. abortus infection in mice. Moreover, Xavier et al [31] showed that the persistent intracellular pathogen B. abortus prevents the immune activation of macrophages by inducing production of an anti-inflammatory cytokine IL-10 from CD4 + CD25 + T cells during early infection time point that modulates macrophage function and contributes to an initial balance between pro-inflammatory and anti-inflammatory cytokines which is beneficial to the pathogen, thereby promoting enhanced bacterial survival.…”

Investigation of CTLA‐4 and CD86 gene polymorphisms in Iranian patients with brucellosis infection

“…Brucella antigens induce production of Th1 proinflammatory cytokines (IFN‐g and TNF‐α) in humans . Recently, it has been demonstrated that the CD28:B7 pathway is important in IFN‐g and TNF‐α production by peripheral blood mononuclear cells from brucellosis patients . The role of this pathway in the immune response is essential, because a signal through CD28 stimulates IL‐2 production and IL‐2R upregulation, leading to T cell proliferation and activation, a process essential to control Brucella multiplication .…”

Perspective of in Vitro Lymphocytes Antigenicity Evaluation for the Diagnostics of Acute Brucellosis

“…По данным ряда авторов перспективными показателями специфической клеточной анти-генреактивности могут выступать следующие маркеры (рецепторы) активации лимфоцитов: CD25 -высокоаффинный рецептор интер-лейкина 2 (IL-2Ra), маркер ранней активации Т-лимфоцитов; HLA-DR -антиген главно-го комплекса гистосовместимости класса II, экспрессия маркера ассоциирована не только с поздней, но и длительной активацией лимфо-цитов; CD95 (Fas, APO-1) -рецептор индукции апоптоза («клеточной смерти»), маркер «позд-ней» активации (представлен преимуществен-но на CD4 + лимфоцитах) и Fas L (CD178) -ре-цептор индукции апоптоза, экспрессируется в основном на CD8 + клетках [11,13,14]. Цель работы -оценить возможность и пер-спективность применения технологии проточ-ной цитофлуориметрии и клеточных тестов in vitrо для диагностики острого бруцеллеза.…”