Ferrer, M Genescà

Fritts, L

Li, J

Ma, M

McChesney, MB

Miller, CJ

English

PubMed

M Genescà  Ferrer

M Ma

J Li

L Fritts

MB McChesney

CJ Miller

Crossref

BioMed CentralPage 1 of 1(page number not for citation purposes)RetrovirologyOpen AccessPoster presentationP01-02. Anti-inflammatory and regulatory mechanisms provide the context for an effective CD8+ T cell response in live-attenuated immunized animalsM Genescà Ferrer*, M Ma, J Li, L Fritts, MB McChesney and CJ MillerAddress: Virology & Immunology, UC Davis – CNPRC/CCM, Davis, CA, USA* Corresponding author    BackgroundLive, attenuated SHIV89.6 immunization protectsmacaques against vaginal challenge with SIVmac239. SIV-specific effector/memory CD8+ T cells, present in thevagina at the time of challenge, mediate this protectionand they do not expand dramatically after challenge.Thus, we hypothesized that the persistent, low-level repli-cation of vaccine virus induces regulatory mechanismswhich maintain a controlled, inflammatory environmentthat does not promote viral replication.MethodsWe assessed CD4+ and CD8+ T regulatory cell frequenciesin the tissues of immunized and unimmunized rhesusmacaques and gene expression of pro-inflammatory andregulatory molecules before and after SIVmac239 vaginalchallenge.ResultsOn the day of challenge, the frequency of circulatingCD4+ T regulatory cells was significantly lower in theimmunized monkeys than in normal controls. However,after challenge (PC), these cells expanded more rapidlyand strongly in lymph nodes (LN) of the immunizedmacaques compared to the control macaques. In addi-tion, at 3 days PC, the frequency of vaginal mucosalCD4+FoxP3+ cells increased in the immunized macaques(p < 0.05). In contrast, the frequencies of CD8+FoxP3+ Tcells in tissues of immunized macaques did not increasePC, as they did in control monkeys. Differences in expres-sion of pro-inflammatory and regulatory genes weredetected in the immunized macaques compared to geneexpression in normal, uninfected macaques at the time ofchallenge. IL-8, IL-17, CCL3 and TNF mRNA levels weresignificantly decreased in LNs and/or vagina of immu-nized macaques. IL-17 mRNA was up-regulated at the siteof challenge on day 7 PC while in SHIV-immunizedmacaques it was down-regulated (p = 0.017). Finally, IL-6increased over-time in tissues of the control, but not theimmunized macaques PC.ConclusionProtection from vaginal challenge in SHIV-immunizedmacaques was associated with expansion of T regulatorycells in tissues but not in blood and down-regulation ofinflammatory molecules, before and immediately afterchallenge.from AIDS Vaccine 2009Paris, France. 19–22 October 2009Published: 22 October 2009Retrovirology 2009, 6(Suppl 3):P2 doi:10.1186/1742-4690-6-S3-P2<supplement> <title> <p>AIDS Vaccine 2009</p> </title> <editor>Anna Laura Ross</editor> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1742-4690-6-S3-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1471-2105-10-S12-info.pdf</url> </supplement>This abstract is available from: http://www.retrovirology.com/content/6/S3/P2© 2009 Ferrer et al; licensee BioMed Central Ltd. 

P01-02. Anti-inflammatory and regulatory mechanisms provide the context for an effective CD8+ T cell response in live-attenuated immunized animals

M Ferrer

Springer - Publisher Connector

BioMed Central
Page 1 of 1
(page number not for citation purposes)
Retrovirology
Open AccessPoster presentation
P01-02. Anti-inflammatory and regulatory mechanisms provide the 
context for an effective CD8+ T cell response in live-attenuated 
immunized animals
M Genescà Ferrer*, M Ma, J Li, L Fritts, MB McChesney and CJ Miller
Address: Virology & Immunology, UC Davis – CNPRC/CCM, Davis, CA, USA
* Corresponding author    
Background
Live, attenuated SHIV89.6 immunization protects
macaques against vaginal challenge with SIVmac239. SIV-
specific effector/memory CD8+ T cells, present in the
vagina at the time of challenge, mediate this protection
and they do not expand dramatically after challenge.
Thus, we hypothesized that the persistent, low-level repli-
cation of vaccine virus induces regulatory mechanisms
which maintain a controlled, inflammatory environment
that does not promote viral replication.
Methods
We assessed CD4+ and CD8+ T regulatory cell frequencies
in the tissues of immunized and unimmunized rhesus
macaques and gene expression of pro-inflammatory and
regulatory molecules before and after SIVmac239 vaginal
challenge.
Results
On the day of challenge, the frequency of circulating
CD4+ T regulatory cells was significantly lower in the
immunized monkeys than in normal controls. However,
after challenge (PC), these cells expanded more rapidly
and strongly in lymph nodes (LN) of the immunized
macaques compared to the control macaques. In addi-
tion, at 3 days PC, the frequency of vaginal mucosal
CD4+FoxP3+ cells increased in the immunized macaques
(p < 0.05). In contrast, the frequencies of CD8+FoxP3+ T
cells in tissues of immunized macaques did not increase
PC, as they did in control monkeys. Differences in expres-
sion of pro-inflammatory and regulatory genes were
detected in the immunized macaques compared to gene
expression in normal, uninfected macaques at the time of
challenge. IL-8, IL-17, CCL3 and TNF mRNA levels were
significantly decreased in LNs and/or vagina of immu-
nized macaques. IL-17 mRNA was up-regulated at the site
of challenge on day 7 PC while in SHIV-immunized
macaques it was down-regulated (p = 0.017). Finally, IL-6
increased over-time in tissues of the control, but not the
immunized macaques PC.
Conclusion
Protection from vaginal challenge in SHIV-immunized
macaques was associated with expansion of T regulatory
cells in tissues but not in blood and down-regulation of
inflammatory molecules, before and immediately after
challenge.
from AIDS Vaccine 2009
Paris, France. 19–22 October 2009
Published: 22 October 2009
Retrovirology 2009, 6(Suppl 3):P2 doi:10.1186/1742-4690-6-S3-P2
<supplement> <title> <p>AIDS Vaccine 2009</p> </title> <editor>Anna Laura Ross</editor> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1742-4690-6-S3-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1471-2105-10-S12-info.pdf</url> </supplement>
This abstract is available from: http://www.retrovirology.com/content/6/S3/P2
© 2009 Ferrer et al; licensee BioMed Central Ltd. 


Miller CJ

McChesney MB

Fritts L

Li J

Ma M

Ferrer M

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P01-02. Anti-inflammatory and regulatory mechanisms provide the context for an effective CD8+ T cell response in live-attenuated immunized animals

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