Destruction of lymphoid organ architecture and hepatitis caused by CD4+ T cells.

Immune responses have the important function of host defense and protection against pathogens. However, the immune response also causes inflammation and host tissue injury, termed immunopathology. For example, hepatitis B and C virus infection in humans cause immunopathological sequel with destructi...

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Autores principales:	Matthias S Matter, Tamara Hilmenyuk, Christina Claus, Romina Marone, Christian Schürch, Marianne Tinguely, Luigi Terracciano, Sanjiv A Luther, Adrian F Ochsenbein
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6b2107be46614b62937adb8ce22240da
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spelling	oai:doaj.org-article:6b2107be46614b62937adb8ce22240da2021-11-04T06:07:56ZDestruction of lymphoid organ architecture and hepatitis caused by CD4+ T cells.1932-620310.1371/journal.pone.0024772https://doaj.org/article/6b2107be46614b62937adb8ce22240da2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21966366/?tool=EBIhttps://doaj.org/toc/1932-6203Immune responses have the important function of host defense and protection against pathogens. However, the immune response also causes inflammation and host tissue injury, termed immunopathology. For example, hepatitis B and C virus infection in humans cause immunopathological sequel with destruction of liver cells by the host's own immune response. Similarly, after infection with lymphocytic choriomeningitis virus (LCMV) in mice, the adaptive immune response causes liver cell damage, choriomeningitis and destruction of lymphoid organ architecture. The immunopathological sequel during LCMV infection has been attributed to cytotoxic CD8(+) T cells. However, we now show that during LCMV infection CD4(+) T cells selectively induced the destruction of splenic marginal zone and caused liver cell damage with elevated serum alanin-transferase (ALT) levels. The destruction of the splenic marginal zone by CD4(+) T cells included the reduction of marginal zone B cells, marginal zone macrophages and marginal zone metallophilic macrophages. Functionally, this resulted in an impaired production of neutralizing antibodies against LCMV. Furthermore, CD4(+) T cells reduced B cells with an IgM(high)IgD(low) phenotype (transitional stage 1 and 2, marginal zone B cells), whereas other B cell subtypes such as follicular type 1 and 2 and germinal center/memory B cells were not affected. Adoptive transfer of CD4(+) T cells lacking different important effector cytokines and cytolytic pathways such as IFNγ, TNFα, perforin and Fas-FasL interaction did reveal that these cytolytic pathways are redundant in the induction of immunopathological sequel in spleen. In conclusion, our results define an important role of CD4(+) T cells in the induction of immunopathology in liver and spleen. This includes the CD4(+) T cell mediated destruction of the splenic marginal zone with consecutively impaired protective neutralizing antibody responses.Matthias S MatterTamara HilmenyukChristina ClausRomina MaroneChristian SchürchMarianne TinguelyLuigi TerraccianoSanjiv A LutherAdrian F OchsenbeinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 9, p e24772 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Matthias S Matter Tamara Hilmenyuk Christina Claus Romina Marone Christian Schürch Marianne Tinguely Luigi Terracciano Sanjiv A Luther Adrian F Ochsenbein Destruction of lymphoid organ architecture and hepatitis caused by CD4+ T cells.
description	Immune responses have the important function of host defense and protection against pathogens. However, the immune response also causes inflammation and host tissue injury, termed immunopathology. For example, hepatitis B and C virus infection in humans cause immunopathological sequel with destruction of liver cells by the host's own immune response. Similarly, after infection with lymphocytic choriomeningitis virus (LCMV) in mice, the adaptive immune response causes liver cell damage, choriomeningitis and destruction of lymphoid organ architecture. The immunopathological sequel during LCMV infection has been attributed to cytotoxic CD8(+) T cells. However, we now show that during LCMV infection CD4(+) T cells selectively induced the destruction of splenic marginal zone and caused liver cell damage with elevated serum alanin-transferase (ALT) levels. The destruction of the splenic marginal zone by CD4(+) T cells included the reduction of marginal zone B cells, marginal zone macrophages and marginal zone metallophilic macrophages. Functionally, this resulted in an impaired production of neutralizing antibodies against LCMV. Furthermore, CD4(+) T cells reduced B cells with an IgM(high)IgD(low) phenotype (transitional stage 1 and 2, marginal zone B cells), whereas other B cell subtypes such as follicular type 1 and 2 and germinal center/memory B cells were not affected. Adoptive transfer of CD4(+) T cells lacking different important effector cytokines and cytolytic pathways such as IFNγ, TNFα, perforin and Fas-FasL interaction did reveal that these cytolytic pathways are redundant in the induction of immunopathological sequel in spleen. In conclusion, our results define an important role of CD4(+) T cells in the induction of immunopathology in liver and spleen. This includes the CD4(+) T cell mediated destruction of the splenic marginal zone with consecutively impaired protective neutralizing antibody responses.
format	article
author	Matthias S Matter Tamara Hilmenyuk Christina Claus Romina Marone Christian Schürch Marianne Tinguely Luigi Terracciano Sanjiv A Luther Adrian F Ochsenbein
author_facet	Matthias S Matter Tamara Hilmenyuk Christina Claus Romina Marone Christian Schürch Marianne Tinguely Luigi Terracciano Sanjiv A Luther Adrian F Ochsenbein
author_sort	Matthias S Matter
title	Destruction of lymphoid organ architecture and hepatitis caused by CD4+ T cells.
title_short	Destruction of lymphoid organ architecture and hepatitis caused by CD4+ T cells.
title_full	Destruction of lymphoid organ architecture and hepatitis caused by CD4+ T cells.
title_fullStr	Destruction of lymphoid organ architecture and hepatitis caused by CD4+ T cells.
title_full_unstemmed	Destruction of lymphoid organ architecture and hepatitis caused by CD4+ T cells.
title_sort	destruction of lymphoid organ architecture and hepatitis caused by cd4+ t cells.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/6b2107be46614b62937adb8ce22240da
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Destruction of lymphoid organ architecture and hepatitis caused by CD4+ T cells.

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