scholarly journals Activation of GABA(A) receptors inhibits T cell proliferation

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251632
Author(s):  
Emma L. Sparrow ◽  
Sonya James ◽  
Khiyam Hussain ◽  
Stephen A. Beers ◽  
Mark S. Cragg ◽  
...  

Background The major sites for fast synaptic inhibition in the central nervous system (CNS) are ion channels activated by γ-aminobutyric acid (GABA). These receptors are referred as GABA(A) receptors (GABA(A)R). Recent evidence indicates a role of GABA(A)R in modulating the immune response. This work aimed to discern the role of GABA and GABA(A)Rs in human and mouse T cell activity. Methods Mouse splenocytes or human peripheral blood mononuclear cells (PBMCs) were activated with anti-CD3 antibodies and the proliferation of both CD8+ and CD4+ T cells assessed through flow cytometry. Subsequently, the effects on T cell proliferation of either GABA(A)R modulation by diazepam that is also capable of activating mitochondrial based translocator protein (TSPO), alprazolam and allopregnanolone or inhibition by bicucculine methiodide (BMI) and (1,2,5,6-Tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) were assessed. Results Positive modulation of GABA(A)Rs either by benzodiazepines or the neurosteroid allopregnanolone inhibits both mouse and human T cell proliferation. GABAergic inhibition of T cell proliferation by benzodiazepines could be rescued by GABA(A)R blocking. Our data suggest that benzodiazepines influence T cell proliferation through both TSPO and GABA(A)Rs activation. Conclusions We conclude that activation of GABA(A)Rs provides immunosuppression by inhibiting T cell proliferation.

1990 ◽  
Vol 2 (6) ◽  
pp. 495-499 ◽  
Author(s):  
M. Djavad Mossalayi ◽  
All H. Dalloul ◽  
Jean-Marc Bertho ◽  
Jean-Claude Lecron ◽  
Patrice Debré

1998 ◽  
Vol 84 (1) ◽  
pp. 53-60 ◽  
Author(s):  
Stephan Kamphuis ◽  
Fredrik Eriksson ◽  
Annemieke Kavelaars ◽  
Jitske Zijlstra ◽  
Marion van de Pol ◽  
...  

1999 ◽  
Vol 372 (1) ◽  
pp. 65-73 ◽  
Author(s):  
Valeria Ayelli Edgar ◽  
Leonor Sterin-Borda ◽  
Graciela A Cremaschi ◽  
Ana M Genaro

Author(s):  
Abby Maizel ◽  
Shashikant Mehta ◽  
Barbara Ruppert ◽  
Richard Ford ◽  
Lawrence Lachman

Author(s):  
Nima Taefehshokr ◽  
Alireza Isazadeh ◽  
Amin Oveisi ◽  
Yashar Azari Key ◽  
Sina Taefehshokr

Abstract Background Human β-defensins (hBD2 and hBD3) are small cationic antimicrobial peptides of innate immune system which can act as a barrier against the majority of pathogens, contributing to the host immune defence. Objective The aim of study is to determine whether hBD2 and hBD3 play a role in development and proliferation of human effector CD4 T cells or not. Furthermore, if enhanced proliferation is observed in the presence of hBD2 and hBD3, these data will demonstrate whether chemokine receptor type 6 (CCR6) is required to be present for this activity to occur. Methods In this study, we examined the effect of hBD2 and hBD3 on CD4+ T cell proliferation in CCR6+ and CCR6− T cells through co-culture of peripheral blood mononuclear cells with anti-CD3 and anti-CD28 stimulation in the presence or absence of hBD2 and hBD3. Proliferation was assessed using flow cytometry. Results It was demonstrated that, co-culture with hBD2 and hBD3 led to up-regulation of CD4+ T cell proliferation after 72 h whereas, CD4+ T cell proliferation was suppressed after 96 h. On the other hand, CCR6− and CCR6+ T cell proliferation was up-regulated after 72 h. But, CCR6+ only was down-regulated in the second cycle in the presence of hBD3. In contrast, after 96 h CCR6+ and CCR6− T cell proliferation was decreased. Conclusion Collectively, our data indicated that hBD2 and hBD3 play a positive and negative regulatory role in development and proliferation of human effector CD4+ T cells which is essential for optimal adaptive immune responses and the control of immunopathology.


2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Rufine Fachinan ◽  
Adnette Fagninou ◽  
Magloire Pandoua Nekoua ◽  
Abdou Madjid Amoussa ◽  
Marius Adjagba ◽  
...  

The mechanism of action of the antidiabetic capacity of Momordica charantia is still under investigation. Here, we assessed phytochemical compositions, antioxidant activity, and effects of total and filtered fruit and leafy stem juices of Momordica charantia on human T cell proliferation and differentiation through quantification of Th1/Th2 cytokines. In the absence of stimulation, total fruit and leafy stem juices induced significant T cell proliferation. Under PHA stimulation, both juices potentiated plant-induced T cell proliferation. However, the filtered fruit and leafy stem juices significantly inhibited PHA-stimulated T cell proliferation, while neither juice influenced T cell proliferation. Moreover, total and filtered fruit juice increased IL-4 secretion, while total and filtered leafy stem juice enhanced IFN-γ production. Phytochemical screening revealed the presence of tannins, flavonoids, anthocyans, steroids, and triterpenoids in both juices. Alkaloids, quinone derivatives, cardenolides, and cyanogenic derivatives were undetectable. The saponins present in total juices were undetectable after filtration. Moreover, both juices had appreciable antioxidant capacity. Our study supports the type 1 antidiabetic effect of filtered fruit juice of M. charantia which may be related to its immunosuppressive and T-helper 2 cell inducing capacities. Due to their immune-stimulatory activities and their ability to increase T-helper 1 cell cytokines, total fruit and leafy stem juices may serve in the treatment of immunodeficiency and certain infections.


Sign in / Sign up

Export Citation Format

Share Document