A role for the chemokine RANTES in regulating CD8 T cell responses during chronic viral infection.

Abstract:

:RANTES (CCL5) is a chemokine expressed by many hematopoietic and non-hematopoietic cell types that plays an important role in homing and migration of effector and memory T cells during acute infections. The RANTES receptor, CCR5, is a major target of anti-HIV drugs based on blocking viral entry. However, defects in RANTES or RANTES receptors including CCR5 can compromise immunity to acute infections in animal models and lead to more severe disease in humans infected with west Nile virus (WNV). In contrast, the role of the RANTES pathway in regulating T cell responses and immunity during chronic infection remains unclear. In this study, we demonstrate a crucial role for RANTES in the control of systemic chronic LCMV infection. In RANTES⁻/⁻ mice, virus-specific CD8 T cells had poor cytokine production. These RANTES⁻/⁻ CD8 T cells also expressed higher amounts of inhibitory receptors consistent with more severe exhaustion. Moreover, the cytotoxic ability of CD8 T cells from RANTES⁻/⁻ mice was reduced. Consequently, viral load was higher in the absence of RANTES. The dysfunction of T cells in the absence of RANTES was as severe as CD8 T cell responses generated in the absence of CD4 T cell help. Our results demonstrate an important role for RANTES in sustaining CD8 T cell responses during a systemic chronic viral infection.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Crawford A,Angelosanto JM,Nadwodny KL,Blackburn SD,Wherry EJ

doi

10.1371/journal.ppat.1002098

subject

Has Abstract

pub_date

2011-07-01 00:00:00

pages

e1002098

issue

7

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-10-00148

journal_volume

7

pub_type

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