CD8<sup>+</sup> T Cell Immunity Is Compromised by Anti-CD20 Treatment and Rescued by Interleukin-17A

ABSTRACT Treatment with anti-CD20, used in many diseases in which B cells play a pathogenic role, has been associated with susceptibility to intracellular infections. Here, we studied the effect of anti-CD20 injection on CD8+ T cell immunity using an experimental model of Trypanosoma cruzi infection...

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Autores principales:	Facundo Fiocca Vernengo, Cristian G. Beccaria, Cintia L. Araujo Furlan, Jimena Tosello Boari, Laura Almada, Melisa Gorosito Serrán, Yamila Gazzoni, Carolina L. Montes, Eva V. Acosta Rodríguez, Adriana Gruppi
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	anti-CD20 B lymphocytes IL-17A T cells Trypanosoma cruzi Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/cb2cab0b6ad84a64815d58f1f221012c
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spelling	oai:doaj.org-article:cb2cab0b6ad84a64815d58f1f221012c2021-11-15T15:56:47ZCD8<sup>+</sup> T Cell Immunity Is Compromised by Anti-CD20 Treatment and Rescued by Interleukin-17A10.1128/mBio.00447-202150-7511https://doaj.org/article/cb2cab0b6ad84a64815d58f1f221012c2020-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00447-20https://doaj.org/toc/2150-7511ABSTRACT Treatment with anti-CD20, used in many diseases in which B cells play a pathogenic role, has been associated with susceptibility to intracellular infections. Here, we studied the effect of anti-CD20 injection on CD8+ T cell immunity using an experimental model of Trypanosoma cruzi infection, in which CD8+ T cells play a pivotal role. C57BL/6 mice were treated with anti-CD20 for B cell depletion prior to T. cruzi infection. Infected anti-CD20-treated mice exhibited a CD8+ T cell response with a conserved expansion phase followed by an early contraction, resulting in a strong reduction in total and parasite-specific CD8+ T cell numbers at 20 days postinfection. Anti-CD20 injection increased the frequency of apoptotic CD8+ T cells, decreased the number of effector and memory CD8+ T cells, and reduced the frequency of proliferating and cytokine-producing CD8+ T cells. Accordingly, infected anti-CD20-treated mice presented lower cytotoxicity of T. cruzi peptide-pulsed target cells in vivo. All of these alterations in CD8+ T cell immunity were associated with increased tissue parasitism. Anti-CD20 injection also dampened the CD8+ T cell response, when this had already been generated, indicating that B cells were involved in the maintenance rather than the induction of CD8+ T cell immunity. Anti-CD20 injection also resulted in a marked reduction in the frequency of interleukin-6 (IL-6)- and IL-17A-producing cells, and recombinant IL-17A (rIL-17A) injection partially restored the CD8+ T cell response in infected anti-CD20-treated mice. Thus, anti-CD20 reduced CD8+ T cell immunity, and IL-17A is a candidate for rescuing deficient responses either directly or indirectly. IMPORTANCE Monoclonal antibody targeting the CD20 antigen on B cells is used to treat the majority of non-Hodgkin lymphoma patients and some autoimmune disorders. This therapy generates adverse effects, notably opportunistic infections and activation of viruses from latency. Here, using the infection murine model with the intracellular parasite Trypanosoma cruzi, we report that anti-CD20 treatment affects not only B cell responses but also CD8+ T cell responses, representing the most important immune effectors involved in control of intracellular pathogens. Anti-CD20 treatment, directly or indirectly, affects cytotoxic T cell number and function, and this deficient response was rescued by the cytokine IL-17A. The identification of IL-17A as the cytokine capable of reversing the poor response of CD8+ T cells provides information about a potential therapeutic treatment aimed at enhancing defective immunity induced by B cell depletion.Facundo Fiocca VernengoCristian G. BeccariaCintia L. Araujo FurlanJimena Tosello BoariLaura AlmadaMelisa Gorosito SerránYamila GazzoniCarolina L. MontesEva V. Acosta RodríguezAdriana GruppiAmerican Society for Microbiologyarticleanti-CD20B lymphocytesIL-17AT cellsTrypanosoma cruziMicrobiologyQR1-502ENmBio, Vol 11, Iss 3 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	anti-CD20 B lymphocytes IL-17A T cells Trypanosoma cruzi Microbiology QR1-502
spellingShingle	anti-CD20 B lymphocytes IL-17A T cells Trypanosoma cruzi Microbiology QR1-502 Facundo Fiocca Vernengo Cristian G. Beccaria Cintia L. Araujo Furlan Jimena Tosello Boari Laura Almada Melisa Gorosito Serrán Yamila Gazzoni Carolina L. Montes Eva V. Acosta Rodríguez Adriana Gruppi CD8<sup>+</sup> T Cell Immunity Is Compromised by Anti-CD20 Treatment and Rescued by Interleukin-17A
description	ABSTRACT Treatment with anti-CD20, used in many diseases in which B cells play a pathogenic role, has been associated with susceptibility to intracellular infections. Here, we studied the effect of anti-CD20 injection on CD8+ T cell immunity using an experimental model of Trypanosoma cruzi infection, in which CD8+ T cells play a pivotal role. C57BL/6 mice were treated with anti-CD20 for B cell depletion prior to T. cruzi infection. Infected anti-CD20-treated mice exhibited a CD8+ T cell response with a conserved expansion phase followed by an early contraction, resulting in a strong reduction in total and parasite-specific CD8+ T cell numbers at 20 days postinfection. Anti-CD20 injection increased the frequency of apoptotic CD8+ T cells, decreased the number of effector and memory CD8+ T cells, and reduced the frequency of proliferating and cytokine-producing CD8+ T cells. Accordingly, infected anti-CD20-treated mice presented lower cytotoxicity of T. cruzi peptide-pulsed target cells in vivo. All of these alterations in CD8+ T cell immunity were associated with increased tissue parasitism. Anti-CD20 injection also dampened the CD8+ T cell response, when this had already been generated, indicating that B cells were involved in the maintenance rather than the induction of CD8+ T cell immunity. Anti-CD20 injection also resulted in a marked reduction in the frequency of interleukin-6 (IL-6)- and IL-17A-producing cells, and recombinant IL-17A (rIL-17A) injection partially restored the CD8+ T cell response in infected anti-CD20-treated mice. Thus, anti-CD20 reduced CD8+ T cell immunity, and IL-17A is a candidate for rescuing deficient responses either directly or indirectly. IMPORTANCE Monoclonal antibody targeting the CD20 antigen on B cells is used to treat the majority of non-Hodgkin lymphoma patients and some autoimmune disorders. This therapy generates adverse effects, notably opportunistic infections and activation of viruses from latency. Here, using the infection murine model with the intracellular parasite Trypanosoma cruzi, we report that anti-CD20 treatment affects not only B cell responses but also CD8+ T cell responses, representing the most important immune effectors involved in control of intracellular pathogens. Anti-CD20 treatment, directly or indirectly, affects cytotoxic T cell number and function, and this deficient response was rescued by the cytokine IL-17A. The identification of IL-17A as the cytokine capable of reversing the poor response of CD8+ T cells provides information about a potential therapeutic treatment aimed at enhancing defective immunity induced by B cell depletion.
format	article
author	Facundo Fiocca Vernengo Cristian G. Beccaria Cintia L. Araujo Furlan Jimena Tosello Boari Laura Almada Melisa Gorosito Serrán Yamila Gazzoni Carolina L. Montes Eva V. Acosta Rodríguez Adriana Gruppi
author_facet	Facundo Fiocca Vernengo Cristian G. Beccaria Cintia L. Araujo Furlan Jimena Tosello Boari Laura Almada Melisa Gorosito Serrán Yamila Gazzoni Carolina L. Montes Eva V. Acosta Rodríguez Adriana Gruppi
author_sort	Facundo Fiocca Vernengo
title	CD8<sup>+</sup> T Cell Immunity Is Compromised by Anti-CD20 Treatment and Rescued by Interleukin-17A
title_short	CD8<sup>+</sup> T Cell Immunity Is Compromised by Anti-CD20 Treatment and Rescued by Interleukin-17A
title_full	CD8<sup>+</sup> T Cell Immunity Is Compromised by Anti-CD20 Treatment and Rescued by Interleukin-17A
title_fullStr	CD8<sup>+</sup> T Cell Immunity Is Compromised by Anti-CD20 Treatment and Rescued by Interleukin-17A
title_full_unstemmed	CD8<sup>+</sup> T Cell Immunity Is Compromised by Anti-CD20 Treatment and Rescued by Interleukin-17A
title_sort	cd8<sup>+</sup> t cell immunity is compromised by anti-cd20 treatment and rescued by interleukin-17a
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/cb2cab0b6ad84a64815d58f1f221012c
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CD8<sup>+</sup> T Cell Immunity Is Compromised by Anti-CD20 Treatment and Rescued by Interleukin-17A

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