Treatment with anti-FasL antibody preserves memory lymphocytes and virus-specific cellular immunity in macaques challenged with simian immunodeficiency virus.

Abstract:

:Immune deficiency viruses such as SIV in macaques or HIV-1 in human beings have evolved mechanisms to defeat host immunity that also impact the efficacy of vaccines. A key factor for vaccine protection is whether immune responses elicited by prior immunization remain at levels sufficient to limit disease progression once a host is exposed to the pathogen. One potential mechanism for escaping pre-existing immunity is to trigger death among antigen-activated cells. We tested whether FasL/CD178 is involved in destroying preexisting immunity. Rhesus macaques were immunized with recombinant vesicular stomatitis virus vaccine expressing SIV Gag to elicit cellular immune responses, then treated with antibody that neutralizes FasL and challenged with intravenous SIVmac251. Compared with animals injected with control antibody, anti-FasL-treated macaques had superior preservation of central memory CD4(+) and CD8(+) cells and decreased regulatory T cells in the blood. The CD4(+) and CD8(+) lymphocytes from treated animals responded better to SIV Gag compared with controls, evidenced by higher cell-mediated immune responses to viral antigens for at least 17 weeks after SIV challenge. Anti-FasL treatment during the initial stages of acute SIV infection preserved the T-cell compartment and sustained cell-mediated immunity to SIV.

journal_name

Blood

journal_title

Blood

authors

Poonia B,Salvato MS,Yagita H,Maeda T,Okumura K,Pauza CD

doi

10.1182/blood-2009-02-202655

subject

Has Abstract

pub_date

2009-08-06 00:00:00

pages

1196-204

issue

6

eissn

0006-4971

issn

1528-0020

pii

blood-2009-02-202655

journal_volume

114

pub_type

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