Hydroxychloroquine reduces T cells activation recall antigen responses

Abstract

Background In the context of the current COVID-19 pandemic, there is still limited information about how people suffering from autoimmune diseases respond to the different COVID vaccines. The fact that they are taking an immunosuppressant or other drugs that aim to decrease the immune system activities, such as hydroxychloroquine (HCQ), could also impact their ability to respond to a COVID vaccine and vaccines in general. Methods Heathy donors were given 200mg of HCQ daily for 6-weeks to assess HCQs impact on the systemic T cells and humoral immune response. Peripheral blood mononuclear cells (PBMC) and plasma were obtained at baseline and 6-weeks after starting daily HCQ. Flow cytometry assays were designed to determine changes in T cell activation and T cell responses. Bead array multiplex were used to analyse antibodies and cytokine levels before and after HCQ intake. Results As anticipated, HCQ treatment decreased ex vivo T cell activation. We observed a decrease in CD4+CD161- expressing CCR5 (p = 0.015) and CD69 (p = 0.004) as well as in CD8+CCR5+ (p = 0.003), CD8+CD161+CCR5+ (p = 0.002) and CD8+CD161+CD95+ (p = 0.004). Additionally, HCQ decreased the proportion of Th17 expressing CD29 (p = 0.019), a subset associated with persistent inflammation. The proportion of T regulatory cells expressing the inhibitory molecule TIGIT was also reduced by HCQ (p = 0.003). As well, T cells from people on HCQ were less responsive to activation and cytokine production following stimulation with recall antigens and memory T cells were less likely to produce both IFNγ and TNFα following stimulation. Conclusion This study shows HCQ is associated with lower T cell activation and decreased T cell cytokine production. While this study was not performed with the intent of looking at COVID vaccine response, it does provide important information about the changes in immune response that may occur in patient taking HCQ as a treatment for their autoimmune disease.

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“…Another mechanism through which HCQ could affect Th17/Treg ratio is by inhibiting autophagy in both cell populations. In experiments with rodents and PBMC isolated from SLE and HIV patients, HCQ attenuated Th17 differentiation, proliferation, and production of IL-17 while promoting the immunosuppressive effect of Tregs ( Piconi et al, 2011 ; An et al, 2017 ; Yang et al, 2018 ; Kowatsch et al, 2023 ). Due to that, An et al suggested that HCQ might have different effects of autophagy on diverse T-cell subsets ( An et al, 2017 ).…”

“…Furthermore, the percentages of plasma cells generated upon in vitro stimulation with CpG were significantly higher in the PE group than in the control group ( Liao et al, 2009 ). These cells present another potential target for HCQ since HCQ effectively suppresses the class-switch of memory B cells to plasma cells and also decreases the production of IgG ( Torigoe et al, 2018 ; Kowatsch et al, 2023 ), both of which are increased in PE ( Liao et al, 2009 ).…”

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“…Mechanistically, HCQ suppresses T-and B-cell receptor mediated signalling by specifically inhibiting calcium signalling and subsequent NFAT (nuclear factor of activated T-cells) activation [108] . HCQ induces apoptosis in autoreactive memory T-cells [109] , and reduces pro-inflammatory T-cell activation [110,111] . 7.…”

Complicaciones De La Vacuna Chadox1 en Pacientes Con Enfermedades Cardiovasculares: Revisión Bibliográfica.

“…(11)(26) (15) También junto con los antivirales se añadió los fármacos antimalárico, como cloroquina o hidrocicloroquina, que demostraron actividad antiviral in vitro. También ha demostrado reducir los niveles de anticuerpos antifosfolípidos y de las células T (CD95) (23) (14) La azitromicina es el antibiótico más usado durante el tratamiento para los pacientes con covid que presentaron infiltrado lobar en una radiografía de tórax, leucocitosis y niveles elevados de LDH sérico. Pero se relacionó con mayores eventos adversos cardiovasculares como insuficiencia cardiaca aguda, lesión renal aguda, insuficiencia respiratoria aguda, pero con un 6,6% riesgo de muerte con el tratamiento estándar.…”