RESUMEN
Tuberculous pleurisy, one of the most common manifestations of extrapulmonary tuberculosis, is characterized by a T-cell-mediated hypersensitivity reaction along with a Th1 immune profile. In this study, we investigated functional cross-talk among T and NK cells in human tuberculous pleurisy. We found that endogenously activated pleural fluid-derived NK cells express high ICAM-1 levels and induce T-cell activation ex vivo through ICAM-1. Besides, upon in vitro stimulation with monokines and PAMP, resting peripheral blood NK cells increased ICAM-1 expression leading to cellular activation and Th1 polarization of autologous T cells. Furthermore, these effects were abolished by anti-ICAM-1 Ab. Hence, NK cells may contribute to the adaptive immune response by a direct cell-contact-dependent mechanism in the context of Mycobacterium tuberculosis infection.
Asunto(s)
Molécula 1 de Adhesión Intercelular/metabolismo , Células Asesinas Naturales/inmunología , Mycobacterium tuberculosis , Linfocitos T/inmunología , Tuberculosis Pleural/inmunología , Adulto , Antígeno CD11a/inmunología , Antígeno CD56/inmunología , Comunicación Celular/inmunología , Cisteína/análogos & derivados , Cisteína/farmacología , Humanos , Molécula 1 de Adhesión Intercelular/efectos de los fármacos , Molécula 1 de Adhesión Intercelular/inmunología , Interleucina-12/farmacología , Interleucina-15/farmacología , Interleucina-18/farmacología , Lipopolisacáridos/farmacología , Lipoproteínas/farmacología , Persona de Mediana Edad , Fosfotransferasas (Aceptor del Grupo Fosfato)RESUMEN
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.