In vitro nonspecific mitogenic response of T-cell subsets in acute and chronic brucellosis

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

“…It seems that chronic relapsing brucellosis patients are unresponsive/anergic to nonspecific or brucellar antigens as it was shown previously [17, 19, 20, 43, 44]. On the other hand, the effect of E. coli on PHA-cultured CD4+/CD28+ T-cells could be attributed to “LPS tolerance phenomenon”, where prior sublethal exposure to LPS results in a state of tolerance to further LPS challenge [45].…”

“…Chronic brucella infection could lead to a defective in vitro blastogenesis of CD4+ T-lymphocytes due to low-proliferation response, reduced production of IFN γ and IL-2, and switching toward Th2 response characterized by an increased percentage of CD3+/IL-13+ T-lymphocytes [17–20]. It had been suggested that IL-13 can downregulate macrophage functions, such as the production of IL-12 and the expression of inducible nitric oxide synthase in response to LPS [19, 41].…”

“…Diminished production of Th1 cytokines (IFN γ and IL-2) has been associated with T-cell unresponsiveness (anergy) to Brucella antigens and disease chronicity [17–19]. In addition, proliferation response of CD4+ T-lymphocytes to phytohaemagglutinin (PHA) in chronic brucellosis patients was found to be significantly low [20]. Recently, we have shown low frequency of ex vivo and PHA-cultured CD4+ T-lymphocytes expressing IL-2 receptor alpha (CD25) in chronic brucellosis patients [21].…”

Diminished percentage of CD4+ T-lymphocytes expressing interleukine-2 receptor alpha in chronic brucellosis

“…14,21 Table 3 Percent proportion of CD3C, CD4C, CD8C T-lymphocytes subsets, as well as percentage of CD25 expression and CD4/CD25 coexpression, in whole peripheral blood in the groups (AB, CB, ''clinically cured'', controls) and CB subgroups (CB1, CB2) studied (results are presented as mean G SD) Recently, the proliferation response of CD4C T-lymphocytes to PHA in chronic brucellosis patients was found to be significantly low compared with those of acute brucellosis patients and controls. 22 In addition, diminished IL-2 production by PBMC after in vitro non-specific mitogenic (PHA) or specific (Brucella antigens) stimulation has been correlated with anergy in brucellosis. 12,13 In accordance to the above, the reduction of the CD4C/IL-2RaC T-cells percent proportion in chronic brucellosis should be the result of Th1/Th2 cytokine network imbalance.…”

Brucella melitensis T Cell Epitope Recognition in Humans with Brucellosis in Peru

“…The clinical manifestations of brucellosis after exposure are usually initiated by cytotoxic immune responses, as surges of cytokines are associated with the destruction of Brucella within infected macrophages. Currently, the mechanisms by which cell-mediated immune responses confer protection and those leading to disease manifestations are unexplained; especially unknown are the reasons why some individuals do not have complications or continuation of acute brucellosis and some develop relapse (11,12).…”