Browsing by Author "Alvarez Salazar, Evelyn Katy"

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Dataset from: Highly purified and functionally stable in vitro expanded allospecific Tr1 cells expressing immunosuppressive graft-homing receptors as new candidates for cell therapy in solid organ transplantation
(Frontiers, 2023-02-24) Arteaga-Cruz, Saúl; Cortés-Hernández, Arimelek; Alvarez Salazar, Evelyn Katy; Rosas-Cortina, Katya; Aguilera-Sandoval, Christian; Morales-Buenrostro, Luis E.; Alberú-Gómez, Josefina M.; Soldevila, Gloria
The development of new strategies based on the use of Tr1 cells has taken relevance to induce long-term tolerance, especially in the context of allogeneic stem cell transplantation. Although Tr1 cells are currently identified by the co-expression of CD49b and LAG-3 and high production of interleukin 10 (IL-10), recent studies have shown the need for a more exhaustive characterization, including co-inhibitory and chemokines receptors expression, to ensure bona fide Tr1 cells to be used as cell therapy in solid organ transplantation. Moreover, the proinflammatory environment induced by the allograft could affect the suppressive function of Treg cells, therefore stability of Tr1 cells needs to be further investigated. Here, we establish a new protocol that allows long-term in vitro expansion of highly purified expanded allospecific Tr1 (Exp-allo Tr1). Our expanded Tr1 cell population becomes highly enriched in IL-10 producers (> 90%) and maintains high expression of CD49b and LAG-3, as well as the co-inhibitory receptors PD-1, CTLA-4, TIM-3, TIGIT and CD39. Most importantly, high dimensional analysis of Exp-allo Tr1 demonstrated a specific expression profile that distinguishes them from activated conventional T cells (T conv), showing overexpression of IL-10, CD39, CTLA-4 and LAG-3. On the other hand, Exp-allo Tr1 expressed a chemokine receptor profile relevant for allograft homing and tolerance induction including CCR2, CCR4, CCR5 and CXCR3, but lower levels of CCR7. Interestingly, Exp-allo Tr1 efficiently suppressed allospecific but not third-party T cell responses even after being expanded in the presence of proinflammatory cytokines for two extra weeks, supporting their functional stability. In summary, we demonstrate for the first time that highly purified allospecific Tr1 (Allo Tr1) cells can be efficiently expanded maintaining a stable phenotype and suppressive function with homing potential to the allograft, so they may be considered as promising therapeutic tools for solid organ transplantation.
Estudio comparativo de la actividad moduladora del extracto metanólico de cuatro ecotipos de Lepidium peruvianum Chacón (maca) sobre la respuesta inmune humoral y celular en ratones
(Universidad Nacional Mayor de San Marcos, 2008) Alvarez Salazar, Evelyn Katy; Alzamora Gonzales, Libertad
Lepidium peruvianum (maca), es un cultivo tradicional de los Andes Centrales del Perú y es empleada desde tiempos precolombinos como una planta medicinal y alimenticia. Los cultivares de maca se diferencian por el color externo de la raíz denominándose a cada uno como ecotipo. Estudios anteriores reportaron que los diferentes ecotipos de maca presentan diferencias en cuanto a su actividad biológica. Los objetivos del presente estudio fueron: Determinar la concentración de flavonoides, calcio y hierro en el extracto metanólico (EM) de los ecotipos blanco, morado, rojo y negro; comprobar la actividad moduladora del EM de los ecotipos blanco, morado, rojo y negro sobre la respuesta inmune humoral in vivo frente a los glóbulos rojos de carnero (GRC) en animales normales e inmunosuprimidos con ciclofosfamida (CF), así como su efecto sobre el peso y celularidad de los órganos linfoides y recuento de las células sanguíneas. Finalmente, determinar la producción de óxido nítrico (ON) por macrófagos peritoneales cultivados con el EM de los ecotipos seleccionados.
Highly purified and functionally stable in vitro expanded allospecific Tr1 cells expressing immunosuppressive graft-homing receptors as new candidates for cell therapy in solid organ transplantation
(Frontiers, 2023-02-23) Arteaga-Cruz, Saúl; Cortés-Hernández, Arimelek; Alvarez Salazar, Evelyn Katy; Rosas-Cortina, Katya; Aguilera-Sandoval, Christian; Morales-Buenrostro, Luis E.; Alberú-Gómez, Josefina M.; Soldevila, Gloria
The development of new strategies based on the use of Tr1 cells has taken relevance to induce long-term tolerance, especially in the context of allogeneic stem cell transplantation. Although Tr1 cells are currently identified by the coexpression of CD49b and LAG-3 and high production of interleukin 10 (IL-10), recent studies have shown the need for a more exhaustive characterization, including co-inhibitory and chemokines receptors expression, to ensure bona fide Tr1 cells to be used as cell therapy in solid organ transplantation. Moreover, the proinflammatory environment induced by the allograft could affect the suppressive function of Treg cells, therefore stability of Tr1 cells needs to be further investigated. Here, we establish a new protocol that allows long-term in vitro expansion of highly purified expanded allospecific Tr1 (Exp-allo Tr1). Our expanded Tr1 cell population becomes highly enriched in IL-10 producers (> 90%) and maintains high expression of CD49b and LAG-3, as well as the coinhibitory receptors PD-1, CTLA-4, TIM-3, TIGIT and CD39. Most importantly, high dimensional analysis of Exp-allo Tr1 demonstrated a specific expression profile that distinguishes them from activated conventional T cells (T conv), showing overexpression of IL-10, CD39, CTLA-4 and LAG-3. On the other hand, Exp-allo Tr1 expressed a chemokine receptor profile relevant for allograft homing and tolerance induction including CCR2, CCR4, CCR5 and CXCR3, but lower levels of CCR7. Interestingly, Exp-allo Tr1 efficiently suppressed allospecific but not third-party T cell responses even after being expanded in the presence of proinflammatory cytokines for two extra weeks, supporting their functional stability. In summary, we demonstrate for the first time that highly purified allospecific Tr1 (Allo Tr1) cells can be efficiently expanded maintaining a stable phenotype and suppressive function with homing potential to the allograft, so they may be considered as promising therapeutic tools for solid organ transplantation.
Producción de mRNA para citoquinas hematopoyéticas (IL-3, GM-CSF e IL-7) en ratones inmunosuprimidos tratados con extracto acuoso de Lepidium meyenii walpers (maca)
(Universidad Nacional Mayor de San Marcos, 2013) Alvarez Salazar, Evelyn Katy; Alzamora Gonzales, Libertad
Determina las propiedades antitumorales e inmunomoduladoras del Lepidium meyenni (maca), que lo convierten en un excelente candidato para investigar su actividad hematopoyética. Se trataron ratones Balb/c a dosis de 200 mg/kg de extracto acuoso (EAc) de maca amarilla por vía oral durante 2 meses previo a la inmunosupresión (IS) con ciclofosfamida (CF), y se evaluó la producción de mRNA para las citoquinas hematopoyeticas: interleuquina 3 (IL-3), factor estimulador de colonias de granulocitos y monocitos (GM-CSF) e interleuquina 7 (IL-7) en el bazo y la médula ósea, tanto en los ratones tratados como en sus controles. Se realizaron cultivos de células mononucleares de médula ósea y se evaluó el efecto del EAc sobre la proliferación celular y producción de mRNA para las 3 citoquinas hematopoyéticas. La administración de EAc en ratones IS, incrementó (p<0.05) la producción de mRNA para las tres citoquinas en el bazo y de IL-7 en la médula ósea, dos días después de la IS; e IL-3 y GM-CSF en la médula ósea 5 días post-IS, al compararlos con los grupos no tratados con el extracto. En cultivos de médula ósea, el EAc en la dosis de 100 µg/ml, estimuló (p<0.05) la proliferación celular y la producción de mRNA para IL-7. Además, los ratones IS y tratados con EAc mostraron mayor recuento de células de médula ósea, sangre periférica, unidades formadoras de colonias endógenas en el bazo (CFU-S) y respuesta proliferativa a mitógenos de los linfocitos, cinco días después de la IS. El EAc de maca estimula la producción de mRNA para las tres citoquinas hematopoyéticas. La administración de EAc a ratones inmunocomprometidos puede revertir los efectos supresores de la ciclofosfamida.