ABSTRACT
La enfermedad injerto versus huésped (EIVH) es una entidad de frecuente presentación en las personas que son intervenidas con alotrasplantes. Es inducida y mantenida por las células inmunocompetentes del injerto, que atacan los tejidos del huésped; especialmente los epitelios. El diagnóstico de la EIVH es clínico, apoyado en la histopatología, pero esta, por sí misma, no permite diagnosticar la entidad. La primera línea de tratamiento de la EIVH continúan siendo los esteroides sistémicos y ante refractariedad para estos, aparecen nuevas terapéuticas que resultan efectivas en casos reportados en la literatura, sin que aún se hayan podido definir guías de manejo para este tipo de pacientes. Se necesita realizar estudios de terapéutica en pacientes refractarios a esteroides para poder concluir al respecto.
Graft versus host disease is a condition of frequent occurrence in people who are implanted with allogeneic transplants. The diagnosis is clinical, supported by histopathology, but this, by itself does not make a diagnosis. The first line of treatment for this entity are systemic steroids. For the patient refractory to systemic steroids, new therapeutics that could be useful are reported, but not yet defined its use and none were superior to steroids. Studies are needed to define the approach to the patient refractory to steroids.
Subject(s)
Humans , Male , Female , Graft vs Host Disease/classification , Graft vs Host Disease/diagnosis , Graft vs Host Disease/history , Graft vs Host Disease/pathology , Graft vs Host Disease/prevention & control , Graft vs Host Disease/therapy , Epithelium , LymphocytesABSTRACT
La enfermedad de Hansen producida por el Mycobacterium leprae, es una enfermedad infecciosa cuyo amplio espectro clínico e inmunopatológico se correlaciona con los diferentes patrones de respuesta Th1/Th2. La activación preferencial de esas subpoblaciones de linfocitos T CD4 juega un rol importante en su patogenia y constituye un modelo natural de esa dicotomía de la respuesta inmune. Ambas formas polares de la lepra presentan un perfil definido de secreción de citoquinas: Th1 (IL2 e IFN?) en el polo tuberculoide y Th2 (IL4, IL5, IL10) en el polo lepromatoso. En el primer caso, la respuesta celular adecuada estimula la activación macrofágica y lleva a la destrucción del bacilo. Las lesiones son escasas y limitadas a la piel y nervios periféricos. En el segundo en cambio, la respuesta celular es casi nula y los bacilos se multiplican descontroladamente dentro de los macrófagos, llevando a la diseminación de las lesiones y afectación de otros órganos. La inmunidad humoral está exacerbada y hay un alto nivel de anticuerpos que no pueden eliminar el germen intracelular. Los factores que determinan la diferenciación hacia una respuesta Th1 ó Th2 no se han esclarecido totalmente. Se han postulado varias hipótesis que hacen referencia a factores genéticos, prevalencia de citoquinas en el microambiente celular, disfunción macrofágica; alteración en los receptores Toll de la inmunidad innata, en la expresión de moléculas coestimulatorias, etc En los últimos años se han descubierto nuevas subpoblaciones de linfocitos, (CD4+ CD25+, Tr1, Th3 y Th17) que estarían implicadas en la desregulación de estas respuestas inmunes.
Hansen' disease, caused by Mycobacterium leprae, is an infectious illness whose wide clinical and immunopathologic spectrum correl with different Th1/Th2 responses patterns. The prefferencial activation of the CD4 T cells subset play an important rol in it's pathogenia and provides a natural model of that balance. Either polars forms present a defwed citokynes secretion profile: Th1 cells (IL-2 and IFN-g) dominate in tuberculoid form, whereas cytokines typically produced by Th2 cells (IL-4, IL-5 and IL-10) dominate in lepromatous form. In the first case, the macrophagic activation kills M leprae. It's lesions are located in nerves and skin only. In the second case, cell-mediated immunity is absent. The bacilli multiply uncontrolably in macrophages and infection is widely disseminated affecting other organs. Humoral immunity is exacerbated and have high levels of antibodies that cannot reach intracellular germ. The factors that determine whether the proliferation CD 4 T cells differentiate into Th1 or Th2 cell are not fully understood. Several hypothesis include genetics factors, prevail of cytokinesin the microenviroment, macrophagic disfunction; alterations in the coestimulatory molecules, on toll receptors of the innate immunity, etc. In recent years times new limphocytes subsets have been discovery (CD4+CD 25+, Tr1, Th3, Th17) that could be implicated in this desregulated immune reponses.
ABSTRACT
Objective To studythe effect of CD+4CD+25 regulatory T(Tr)cells on dendric cells(DC)in peripheral blood and deciduas from unexplained recurrent spontaneous abortion(URSA)patients.Methods Four URSA patients(abortion group)and 4 normal early pregnant women(control group)were enrolled in this study.Tr cells and DC in the peripheral blood and deciduas were isolated using Ficoll density gradient centrifugation and magnetic cell sorting(MACS).DC were cultured alone(DC alone)or in combination with Tr cells(DC+Tr)for 6 days,during which the release of interferon(IFN)-γandinterleukin(IL)-10 in the medium was subsequently measured by enzyme linked immunoadsorbent assay (ELISA).Results(1) Peripheral blood:there was no significant difference in IFN-γlevel between DCalone(23.2±0.7)ng/L and DC+Tr(22.5±3.0)ng/L in abortion group(P>0.05).The similar level of IL-10 was observed between DC alone(37±7)ng/L and DC+Tr(35±4)ng/L in abortion group(P>0.05).IL-10 level,but not IFN-γ,was significantly hisber in DC alone(54±20)ns/L than that in DC+ Tr(36±9)ng/L in control group(P<0.01).(2)Deciduas:there was no significant difference in IFN-γlevel between DC alone(23.4±2.6)ng/L and DC+Tr(24.4±2.5)ng/L in abortion group(P>0.05).Moreover,Similar IL-10 level was found between DC alone(28±7)ng/L and DC+Tr(25±5)ng/L in abortion group(P>0.05).IFN-γlevel in CD alone(30.7±4.6)ng/L was significantly higher than that in DC+Tr(22.6±3.8)ng/L in control group(P<0.01);whereas IL-10 level was much lower in DC alone (27±6)ng/L than that in DC+Tr(31±9)ng/L in control group(P<0.05).Conclusion The decreasing of immunosuppressive funetion of Tr eell of URSA patients affect its regulation on DC.resulting in imbalance of Th1/Th2 and abnormality of maternal-fetal jmmuno-tolerence in URSA.
ABSTRACT
Objective To study the inhibitory effect on the expression of regulated upon activation,normal T cell expressed and secreted (RANTES) and monocyte ehemotactic activity of ectopic endometrial stromal cells by nuclear factor(NF)-kB decoy oligonucleotides (ODN). Methods The stromal cells of ectopic endometrium were divided into 3 groups. Two groups were cultured with or without 10 μg/L of interleukin (IL)-1β. Another group was transfected with NF-kB decoy ODN with the aid of a lipofectamine reagent. After 4 h of transfection, 10 μg/L of IL-1β was added to induce the stromal cells to secrete RANTES. Concentration of RANTES in the supernatant at 4, 8, 12, 24 and 36 h was measured with the sandwich enzyme linked immunosorbent assay (ELISA). U937 monocyte chemotactic activity was assayed in Boyden chambers. The specific RANTES-neutralizing monoclonal antibodies at serial doses (0. 5, 1, 2, 4and 8 mg/L) were added into IL-1β induced medium of 24 h to detect the monocyte chemotactic activity of RANTES in supernatant. Results The concentration of RANTES secreted by stromal cells was respectively (58 ± 10), ( 150 ± 35 ), ( 360 ± 46 ) and ( 586 ± 42 ) ng/L after IL-1β stimulation for 8,12,24 and 36 h,significantly higher than that of stromal cells cultured without IL-1β. The concentrations of RANTES were respectively (86±16), ( 128±28 ) and ( 183±32) ng/L after IL-1β stimulation for 12, 24 and 36 h in stromal cells transfected with NF-kB decoy ODN, evidently lower than that of stromal cells stimulated with IL-1β alone. The monocyte ehemotactic index of 12, 24, 36 h in conditioned medium of stromal cells transfected with NF-kB decoy ODN was respectively 10. 3 ± 0. 9, 13.7 ± 1.1, 18.6 ± 1.2, which was evidently lower than that of stromal cells stimulated with IL-1β alone. The anti-RANTES antibody at 0. 5, 1,2, 4 and 8 mg/L inhibited respectively 5%, 23%, 40%, 62% and 61% of the chemotactic activity in 12 h medium treated with IL-1β. Conclusions RANTES accounts for the majority of the monocyte chemotactic activity in IL-1β induced medium of 24 h. NF-kB decoy ODN may influence the feed-forward inflammatory loop whereby IL-1β from activated macrophages can lead to RANTES production by ectopic implants and further monocyte chemotaxis.