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During the innate immune response against infections, Natural Killer (NK) cells are as important effector cells as are Cytotoxic T lymphocytes (CTL) generated after antigenic stimulation in the adaptative response. NK cells increase in numbers, after viral infection or vaccination. We investigated the NK cell and CD8 T lymphocyte status in 55 dengue infected patients. The NK (CD56+CD3-) and CD56+ T cell (CD56+CD3+) rates rise during the acute phase of disease. The majority of NK cells from dengue patients display early markers for activation (CD69, HLA-DR, and CD38) and cell adhesion molecules (CD44, CD11a) during the acute phase of disease. The intracellular cytotoxic granule, TIA-1, is also up-regulated early in NK cells. Most of these markers appear also on CD8+ T lymphocytes but during the late acute phase. Circulating IL-15 is elevated in a significant number of patients during early acute infection and its values were statistically correlated with NK frequencies and cytotoxic markers on NKs. We have therefore shown that dengue virus infection is very likely stimulating a cytotoxic response that may be efficient in controlling the virus in synergism with CD8+ T lymphocytes. Interestingly, the heightened CD56+CD3-, CD56+CD3+, CD56+TIA-1+ and CD56+CD11a+ cell rates are associated with mild dengue clinical manifestations and might indicate a good prognosis of the disease. [ABSTRACT FROM AUTHOR]

The neuropeptide substance P (SP) is known to increase cell-mediated immune responses in animal models and healthy subjects. Several studies have suggested an involvement of neuropeptides in the immunopathogenesis of some diseases. The study of the immunomodulatory effects of neuropeptides, namely SP, may represent a model for the analysis of immunoregulatory defects in HIV infection at the level of the interaction between the immune and nervous systems, both of which are known to be affected by the virus. In the present study, we investigate the possibility of a disturbance in the immunomodulatory properties of SP in HIV infection by analysing the effects of SP (10-10-10-6 M) on the lymphocyte proliferative responses to concanavalin A (Con A) and phytohaemagglutinin (PHA) assessed by ³H-thymidine incorporation in peripheral blood lymphocytes from 34 HIV-infected patients (16 asymptomtic (ASY)/persistent generalized lymphadenopathy(PGL); 18 ARC/AIDS) and in 37 healthy subjects. In ASY PGL HIV-infected patients, SP 10-7 M was identified as the concentration inducing the maximal increase in the lymphocyte responses to Con A and PHA, similarly to what was observed in healthy subjects. In ARC/AIDS patients, SP appeared to inhibit the mitogenic responses, particularly those induced by Con A, in contrast to the effects found either in healthy subjects or in ASY/PGL patients. These results suggest the existence of an alteration in the in vitro immunomodulatory properties of SP in ARC/AIDS patients compared with healthy subjects and ASY/PGL patients. In conclusion, the unexpected finding of an inhibitory effect of SP on lymphocyte proliferation from ARC/AIDS patients justifies further investigation of the neuropeptide-dependent immunoregulatory systems in HIV infection. [ABSTRACT FROM AUTHOR]

Lymphocyte reactivity to drugs is present in a majority of cases of drug-induced liver injury when in vitro proliferation assays to the suspected drugs are used. One possible explanation to this could be that adherent suppressor cells mediating their action through the production of prostaglandin E2 would suppress the lymphocyte proliferation to drugs in vitro. We studied 42 patients with a clinical diagnosis of drug-induced liver injury by comparing lymphocyte proliferation observed in cultures with five different concentrations of the suspected drug with the lymphocyte proliferation observed in cultures with drug and a prostaglandin inhibitor (indomethacin). Forty-four healthy subjects and 15 individuals with a recent exposure to the suspected drug without development of adverse drug reactions were also studied as controls. In nine (21%) out of 42 patients with drug-induced liver injury a significant lymphocyte reactivity to drugs was detected. When a prostaglandin inhibitor was added to the cultures, the detection of lymphocyte reactivity increased from 21% to 57%. No cases of lymphocyte reactivity to drugs or drugs with prostaglandin inhibitor were found in the control groups. The phenomenon of increase of lymphocyte proliferation with the addition of a prostaglandin inhibitor was more frequent in patients whose hepatitis was cured in less than 2 months, was more frequently found in certain pharmacological groups and was significantly associated to a latency period to development of hepatitis of less than 8 days. In conclusion, the in vitro phenomenon described here may be used to improve the ability to demonstrate lymphocyte sensitization in drug-induced liver injury and the clinical correlations found are consistent with the possibility of its relevance in vivo. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV)-specific CD8+ T cell responses do not protect against reinfection. Activation of mammalian target of rapamycin (mTOR) impairs memory CD8+ T cell differentiation. Our hypothesis was that RSV inhibits the formation of CD8+ T cells memory responses through mTOR activation. To explore this, human and mouse T cells were used. RSV induced mTOR phosphorylation at Ser2448 in CD8 T cells. mTOR activation by RSV was completely inhibited using rapamycin. RSV-infected children presented higher mTOR gene expression on nasal washes comparing to children infected with metapneumovirus and rhinovirus. In addition, RSV-infected infants presented a higher frequency of CD8+ pmTORser2448+ T cells in nasal washes compared to RSV-negative infants. Rapamycin treatment increased the frequency of mouse CD8 RSV-M282-90 pentamer-positive T cells and the frequency of RSV-specific memory T cells precursors. These data demonstrate that RSV is activating mTOR directly in CD8 T cells, indicating a role for mTOR during the course of RSV infection. [ABSTRACT FROM AUTHOR]