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

Matter, Matthias S; Hilmenyuk, Tamara; Claus, Christina; Marone, Romina; Schürch, Christian; Tinguely, Marianne; Terracciano, Luigi; Luther, Sanjiv A; Ochsenbein, Adrian (2011). Destruction of lymphoid organ architecture and hepatitis caused by CD4+ T cells. PLoS ONE, 6(9), e24772. Lawrence, Kans.: Public Library of Science 10.1371/journal.pone.0024772

[img]
Preview
Text
journal.pone.0024772.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (5MB) | Preview

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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie

04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Autopsy
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

UniBE Contributor:

Hilmenyuk, Tamara; Claus, Christina; Schürch, Christian; Terracciano, Luigi and Ochsenbein, Adrian

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1932-6203

Publisher:

Public Library of Science

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:20

Last Modified:

10 Jul 2015 11:34

Publisher DOI:

10.1371/journal.pone.0024772

PubMed ID:

21966366

Web of Science ID:

000295267100008

BORIS DOI:

10.7892/boris.6458

URI:

https://boris.unibe.ch/id/eprint/6458 (FactScience: 211424)

Actions (login required)

Edit item Edit item
Provide Feedback