The Th17/Treg ratio, IL-1RA and sCD14 levels in primary HIV infection predict the T-cell activation set point in the absence of systemic microbial translocation.

Impairment of the intestinal barrier and subsequent microbial translocation (MT) may be involved in chronic immune activation, which plays a central role in HIV pathogenesis. Th17 cells are critical to prevent MT. The aim of the study was to investigate, in patients with primary HIV infection (PHI), the early relationship between the Th17/Treg ratio, monocyte activation and MT and their impact on the T-cell activation set point, which is known to predict disease progression. 27 patients with early PHI were included in a prospective longitudinal study and followed-up for 6 months. At baseline, the Th17/Treg ratio strongly negatively correlated with the proportion of activated CD8 T cells expressing CD38/HLA-DR or Ki-67. Also, the Th17/Treg ratio was negatively related to viral load and plasma levels of sCD14 and IL-1RA, two markers of monocyte activation. In untreated patients, the Th17/Treg ratio at baseline negatively correlated with CD8 T-cell activation at month 6 defining the T-cell activation set point (% HLA-DR(+)CD38(+) and %Ki-67(+)). Soluble CD14 and IL-1RA plasma levels also predicted the T-cell activation set point. Levels of I-FABP, a marker of mucosal damages, were similar to healthy controls at baseline but increased at month 6. No decrease in anti-endotoxin core antibody (EndoCAb) and no peptidoglycan were detected during PHI. In addition, 16S rDNA was only detected at low levels in 2 out 27 patients at baseline and in one additional patient at M6. Altogether, data support the hypothesis that T-cell and monocyte activation in PHI are not primarily driven by systemic MT but rather by viral replication. Moreover, the "innate immune set point" defined by the early levels of sCD14 and IL-1RA might be powerful early surrogate markers for disease progression and should be considered for use in clinical practice.

Level of double negative T cells, which produce TGF-ß and IL-10, predicts CD8 T-cell activation in primary HIV-1 infection.

OBJECTIVE: Persistent immune activation plays a central role in the pathogenesis of HIV disease. Besides natural regulatory T cells (nTregs), 'double negative' T cells shown to exhibit regulatory properties could be involved in the control of harmful immune activation. The aim of this study was to analyze, in patients with primary HIV infection (PHI), the relationship between CD4(+)CD25(+)CD127(low)FoxP3(+) nTregs or CD3(+)CD4(-)CD8(-) double negative T cells and systemic immune activation. DESIGN: A prospective longitudinal study of patients with early PHI. METHODS: Twenty-five patients were included. Relationships between frequency of Treg subsets and T-cell activation, assessed on fresh peripheral blood mononuclear cells, were analyzed using nonparametric tests. Cytokine production by double negative T cells was assessed following anti-CD3/anti-CD28 stimulation. RESULTS: No relationship was found between T-cell activation and frequencies of nTregs. In contrast, a strong negative relationship was found at baseline between the proportion of double negative T cells and the proportion of activated CD8 T cells coexpressing CD38 and HLA-DR (P = 0.005) or expressing Ki-67 (P = 0.002). In addition, the frequency of double negative T cells at baseline negatively correlated with the frequency of HLA-DR(+)CD38(+)CD8(+) T cells at month 6, defining the immune activation set point (P = 0.031). High proportions of stimulated double negative T cells were found to produce the immunosuppressive cytokines transforming growth factor-ß1 and/or IL-10. CONCLUSION: The proportion of double negative T cells at baseline was found to be predictive of the immune activation set point. Our data strongly suggest that double negative T cells may control immune activation in PHI. This effect might be mediated through the production of TGF-ß1/IL-10 known to downmodulate immune activation.

Foscarnet as salvage therapy in HIV-2-infected patient with antiretroviral treatment failure.

Previous studies have suggested the efficacy of foscarnet combined with thymidine analogues as salvage therapy in late-stage HIV-1 infection. Here, we report on the first case of foscarnet therapy in a patient infected with HIV-2 exhibiting virologic failure. The patient was known to be HIV-2-infected since 1992 and had received 11 sequential lines of combined antiretroviral therapy (cART) with almost all the available antiretroviral agents including raltegravir. A marked decrease in HIV-2 plasma viral load of 1.48 log(10)copies/ml was observed at day 14 of foscarnet induction therapy associated with zidovudine and failing cART. An optimized cART was then introduced with lamivudine, zidovudine, lopinavir/r, etravirine and maraviroc. Four months after the end of foscarnet therapy, HIV-2 plasma viral load remained undetectable. This case report suggests that foscarnet may represent a therapeutic option for HIV-2-infected patients exhibiting multidrug resistance.

Increased expression of CD154 and FAS in SLE patients' lymphocytes.

An increased level of apoptotic material and B cell activation leading to autoantibody production are hallmarks of systemic lupus erythematoses (SLE). Increased FAS expression, apoptosis, and CD154-mediated signaling, enabling T­B cell interaction are involved in the pathogenesis of SLE. This study addresses the expression profile of CD154 and FAS in the peripheral blood of patients with SLE, rheumatoid arthritis (RA) and normal healthy control donors. Surface markers on peripheral blood T and B cells from patients and healthy control donors were assessed using flow cytometry. The expression of CD154 and FAS were significantly increased in T and B cells of SLE patients as compared to healthy control donors and RA patients. In SLE and RA patients, FAS expression strongly correlated with CD154 expression on T cells, which was not found in healthy control donors. FAS expression was also associated with the occurrence of anti-DNA antibodies. We demonstrate high CD154 and FAS expression as a characteristic feature of SLE. This pattern may reflect simultaneous activation of apoptosis and activation of B­T cell interaction in SLE.