ABSTRACT
Cough variant asthma （CVA） is a chronic respiratory disease with cough as its main symptom. The occurrence of CVA is closely related to non-specific airway inflammation， and its pathogenesis involves environmental， genetic， immune， and other factors. In recent years， the advantages of traditional Chinese medicine （TCM） in the treatment of CVA have attracted the attention of experts and scholars in China and abroad， especially its prominent role in regulating immune balance， relieving cough symptoms in CVA patients， and reducing recurrence. T Helper cells 1 （Th1）， T helper cells 2 （Th2）， T helper cells 17 （Th17）， and regulatory T cells （Treg） are derived from CD4+ T cells. Immune imbalance of Th1/Th2 and Th17/Treg is a new hotspot in the pathogenesis of CVA and a potential key target in the treatment of CVA by TCM. Th cell subsets are in dynamic balance under physiological conditions， maintaining respiratory immune homeostasis in which pro-inflammatory cytokines and anti-inflammatory cytokines are balanced. Immature helper T cells （Th0） can be differentiated into Th1， Th2， Th17， Treg， and other cell subsets due to cytokine types in the microenvironment in the stage of CVA maturation. The proliferation of Th2 cells leads to eosinophilic airway inflammation. Excessive differentiation of Th17 cells induces neutrophil airway inflammation. Th1/Th2 and Th17/Treg cells are mutually restricted in number and function， and the immune imbalance of Th1/Th2 and Th17/Treg is easy to aggravate the generation of inflammatory response. Restoring immune balance is particularly important for the airway anti-inflammatory therapy of CVA. In this paper， the imbalance of Th1/Th2 and Th17/Treg and the pathogenesis of CVA were systematically expounded. Meanwhile， the latest research on the regulation of immune imbalance by TCM compound， single TCM， and its effective ingredients in the treatment of CVA was reviewed. It provides ideas and references for revealing the scientific connotation of TCM regulating immune balance therapy of CVA， as well as the development of clinical treatment and basic research of CVA.
ABSTRACT
Introducción: El Herpes Labial Recurrente supone una condición inmunológica alterada, tal como una hiperactividad de células T-reguladoras CD4+CD25+ (Treg). Éstas ejercen control sobre la tolerancia periférica y reducen el riesgo inmunopatológico, suprimiendo otras líneas celulares. Por ende, la supresión ejercida sobre la reacción inmune antiviral podría afectar negativamente el curso de la infección. Este contexto ha impulsado la búsqueda de nuevas alternativas inmunomoduladoras como la Equinácea purpúrea. Dada su propiedad inmunosupresora, se propone en el tratamiento del Herpes Labial Recurrente. Metodología: Estudio clínico prospectivo que analiza las subpoblaciones linfocitarias en 12 pacientes con Herpes Labial Recurrente, antes y después de recibir Equinácea purpúrea (30 gotas tres veces al día durante siete días).Resultados: En comparación con individuos sanos, los pacientes presentan una respuesta aumentada de células Treg. Esta condición se reduce significativamente tras recibir Equinácea purpúrea (515 + 145 y 432 + 113 cel/mm3 antes y después del tratamiento, respectivamente, p < 0,005). Conclusión: La hiperactividad de células Treg podría explicar el estado de inmunosupresión de estos pacientes y favorecería la persistencia viral. Se propone esta fitomedicina como una alternativa inmunoterapéutica beneficiosa.
Background: Recurrent Herpes Labialis patients may suffer from immunological alterations, such as CD4+CD25+Regulatory-T Cell (Treg) hyperactivity. These cells control peripheral tolerance and reduce immunopathology risk by suppressing other immunological cells. Hence, the Treg cell suppression on the antiviral immune reaction may perturb adversely the herpes infection outcome. This scenario has forced physicians to explore new immunomodulatory alternatives in Phytomedicine, such as Echinacea purpurea. Regarding the immunosuppressive property, it has been challenged to be employed in the Recurrent Herpes Labialis management. Methods: Clinical prospective study that analyzed lymphocytic subpopulation profile in twelve patients with Recurrent Herpes Labialis, before and after receiving E. purpurea (30 drops three times a day during seven days). Results: Comparing to healthy subjects, patients presented an enlarged Treg cell response. This condition became significantly reduced after receiving E. purpurea. (515 + 145 and 432 + 113 cel, before and after treatment respectively, p < 0.005). Conclusion: The intensified Treg cell activity may elucidate the immune suppression these patients undergo, aiding the viral persistence and survival. This proposes E. purpurea asa beneficial immunotherapeutic alternative.
Subject(s)
Humans , Antiviral Agents/therapeutic use , Echinacea/therapeutic use , Echinacea/chemistry , Herpes Labialis/drug therapy , Plant Preparations/therapeutic use , Antiviral Agents/pharmacology , Echinacea/pharmacology , Herpes Labialis/immunology , Herpes Simplex/drug therapy , Herpesvirus 1, Human , Immunomodulation , Multicenter Studies as Topic , Prospective Studies , Plant Preparations/pharmacology , Recurrence/prevention & control , T-Lymphocytes, RegulatoryABSTRACT
Objective To explore the role of CD4+CD25+regulatory T cells(Treg)in the co-culture svstem consisting of T cells and mouse embryo fibroblasts(MEF)infected with murine cytomegalovirus (MCMV)in vitro.Methods A co-culture system of T cells and MCMV infected MEF(MEFMCMV)was established.The viral load in the supernatants was determined by plaque assay.TH1/TH2 differentiation-specific transcription factors T-bet/GATA-3 were assayed by Western blot.The levels of cytokines IL-4,IL-10and IFN-γ in the co-culture supenatants were measured by double-antibody sandwich ELISA.Results After 3 d incubation,the viral load in the supernatants of TdepTreg-MEFMCMC group,in which the T cells depleted Treg(TdepTreg)were co-cultured together with MEFMVMV,was significantly lower than that in MEFMCMV group.And in the co-cultivation of MEFMCMV and T cells without Treg the expressions of T-bet/GATA-3,IL-4,IL-10 and IFN-γ incteased significantly.Compared with the virus content in the TdepTreg-MEFMCMV group,the MCMV load in the"add-on Treg group"increased and the levels of T-bet/GATA-3 and IFN-γ were lower,and the expression of IL-4 didn't show any significant difference. Compared with the level of IL-10 in the TdepTreg-MEFMCMV group,the IL-10 level in the"add-on TREG group"didn't show any significant differece when the Treg ratio among total T cells was 1%～2%,and increased significantly when the Treg ratio was more than 5%.These eflfects were all correlated with Treg ratios in a dose-dependent manner.Conclusion MCMV infected MEF can induce the proliferation and activation of effector T cells,but Treg can inhibit the T cell-mediated protective effect on MCMV infection.
ABSTRACT
Objective:To investigate the role of recombinant E.coli LLO/OVA on regulating the function of murine CD4+ CD25+ Treg cells.Methods:After E.coli LLO/OVA or E.coli OVA vaccination,the murine spleen CD4+ CD25+ Treg,CD4+ CD25- T and CD11c cells were collected respectively by magnetic beads sorting.The concentration of IL-10 in the supernatant of mix cocultured CD4+ CD25+ Treg and CD11c cells,and the suppression role of CD4+ CD25+ Treg cells on the proliferation of CD4+ CD25- T cells were determined.The percentage of OVA specific CD8+ T cells in mouse spleen was analyzed by flow cytometry.The number of metastatic tumor nodules in lungs of the mice transplanted with B16-OVA subcutaneouly was compared before and after dilition of CD4+ CD25+ Treg cells in mice.Results:Compared to E.coli OVA,E.coli LLO/OVA significantly downregulated IL-10 secretion of CD4+CD25+Treg cells and attenuated the suppressive effect of CD4+ CD25+ Treg on the proliferation of CD4+ CD25- T cells(P