In allergy and asthma, the fine balance between the T helper (Th) 1, Th2 and T regulatory cytokine responses appears to be shifted towards Th2. Here, we report that synthetic lipopeptides which contain the typical lipid part of the lipoprotein of gram-negative bacteria stimulate a distinct regulatory cytokine pattern and inhibit several Th2 cell-related phenomena. The most potent analogue of synthetic lipopeptides, lipopeptide CGP 40774 (LP40) was not active in MyD88-deficient mice and stimulated Toll-like receptor (TLR)-2, but not TLR-4. LP40 potentiated the production of IFN-+ and IL-10, but not IL-4 and IL-5 by human T cells. In addition, triggering of TLR-2 by lipopeptides promoted the in vitro differentiation of naive T cells towards IL-10-and IFN-+ -producing T cells and suppressed IL-4 production by Th2 cells. Accordingly, LP40 inhibited IgE production induced by allergen, anti-IgD antibody, Nippostrongylus brasiliensis or murine acquired immunodeficiency virus. Furthermore, ovalbumin-induced lung eosinophilic inflammation was abolished and Schistosoma mansoni egg-induced granuloma size and eosinophil counts were suppressed in mice by LP40. These results demonstrate that stimulation of TLR-2 by lipopeptides represents a novel way for possible treatment of allergy and asthma by regulating the disrupted cytokine balance.

CD4 T-cell depletion in HIV-1 infection is partly the result of T-cell apoptosis. Spontaneous apoptosis (SA) and apoptosis markers Fas-associated death-domain-like IL-1 beta converting enzyme (FLICE)-like inhibitory protein (FLIP), Bcl-2, TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), TRAIL receptor 1, and Fas were determined in 55 HIV-1 infected persons treated with highly active antiretroviral therapy (HAART) for 48 months. Despite suppressive HAART, SA remained elevated. Increased SA of peripheral blood mononuclear cells (PBMCs) and CD8 T lymphocytes and increased TRAIL receptor 1 expression strongly predicted a poorer recovery of CD4 T-cell count. HAART did not significantly alter anti-or proapoptotic markers in cultured PBMCs and T lymphocytes. The significant relationship between residual T-lymphocyte apoptosis and CD4 T-cell recovery suggests that persistent apoptosis may impede immune restoration.