The paradox of a persistent immune response against a latent infection

[Guest guest]

Am J Pathol. 2003 Dec;163(6):2179-84.

Latent herpesvirus infection in human trigeminal ganglia causes chronic

immune response.

Theil D, Derfuss T, Paripovic I, Herberger S, Meinl E, Schueler O,

Strupp M, Arbusow V, Brandt T. Department of Neurology, Klinikum

Grosshadern, Ludwig-Maximilians University, Munich, Germany.

dtheil@...

The majority of trigeminal ganglia (TGs) are latently infected with

alpha-herpesviruses [herpes simplex virus type-1 (HSV-1) and

varicella-zoster virus (VZV)]. Whereas HSV-1 periodically reactivates in the

TGs, VZV reactivates very rarely. The goal of this study was to determine

whether herpesvirus latency is linked to a local immune cell infiltration in

human TGs. T cells positive for the CD3 and CD8 markers, and CD68-positive

macrophages were found in 30 of 42 examined TGs from 21 healthy individuals.

The presence of immune cells correlated constantly with the occurrence of

the HSV-1 latency-associated transcript (LAT) and only irregularly with the

presence of latent VZV protein. In contrast, uninfected TGs showed no immune

cell infiltration. Quantitative RT-PCR revealed that CD8, interferon-gamma,

tumor necrosis factor-alpha, IP-10, and RANTES transcripts were

significantly induced in TGs latently infected with HSV-1 but not in

uninfected TGs. The persisting lymphocytic cell infiltration and the

elevated CD8 and cytokine/chemokine expression in the TGs demonstrate for

the first time that latent herpesviral infection in humans is accompanied by

a chronic inflammatory process at an immunoprivileged site but without any

neuronal destruction. The chronic immune response seems to maintain viral

latency and influence viral reactivation.

Publication Types:

* Research Support, Non-U.S. Gov't

PMID: 14633592 [PubMed - indexed for MEDLINE]

12: J Immunol. 1996 Oct 15;157(8):3542-9.

Persistent cytokine expression in trigeminal ganglion latently infected

with herpes simplex virus type 1.

Halford WP, Gebhardt BM, Carr DJ. Department of Microbiology,

Louisiana State University Medical Center, New Orleans 70112, USA.

Following ocular infection, herpes simplex virus type 1 (HSV-1)

establishes latency in trigeminal ganglion (TG) neurons. Using reverse

transcription-PCR, cytokine gene expression was analyzed in the TGs of mice

infected with HSV-1. IL-2, TNF-alpha, IFN-gamma, IL-10, and RANTES mRNAs

were readily detected in TGs taken from mice 7 days postinoculation (PI).

Likewise, IL-2, IL-6, IL-10, and IFN-gamma protein were detected by ELISA of

TG homogenates. Between 5 and 45 days PI, IL-10, IFN-gamma, TNF-alpha, and

RANTES mRNAs were detected in nearly 100% of latently infected TGs (latent

infection was confirmed by reverse transcription-PCR detection of HSV-1

latency-associated transcripts). T cell-associated cytokine and chemokine

mRNAs (IL-2, IL-10, IFN-gamma, and RANTES) were still detected in the

majority of latently infected TG samples taken between 60 and 135 days PI.

In contrast, these cytokine mRNA species were rarely detected in uninfected

TGs. Measurement of serum Abs to HSV-1 at different times revealed that

anti-HSV-1 Ab concentrations approached a plateau in mice by 30 days PI but

remained at high levels 67 and 125 days PI. Although there was molecular

evidence of an ongoing immune response to HSV-1 in latently infected TG,

histologic analysis indicated that very few mononuclear cells remained in

the ganglion 60 days PI. Collectively, the results suggest that residual

lymphocytes encounter viral Ag during HSV-1 latency with sufficient

frequency to remain activated. The paradox of a persistent immune response

against a latent infection is discussed.

Publication Types: PMID: 8871654

------ End of Forwarded Message

[Guest guest]

I hope this is true.... " is accompanied by a chronic inflammatory process at an

immunoprivileged site but without any neuronal destruction. "

JR

From: neno@...

Date: Wed, 10 Jun 2009 12:05:51 +0100

Subject: The paradox of a persistent immune response against a latent

infection

Am J Pathol. 2003 Dec;163(6):2179-84.

Latent herpesvirus infection in human trigeminal ganglia causes chronic

immune response.

Theil D, Derfuss T, Paripovic I, Herberger S, Meinl E, Schueler O,

Strupp M, Arbusow V, Brandt T. Department of Neurology, Klinikum

Grosshadern, Ludwig-Maximilians University, Munich, Germany.

dtheil@...

The majority of trigeminal ganglia (TGs) are latently infected with

alpha-herpesviruses [herpes simplex virus type-1 (HSV-1) and

varicella-zoster virus (VZV)]. Whereas HSV-1 periodically reactivates in the

TGs, VZV reactivates very rarely. The goal of this study was to determine

whether herpesvirus latency is linked to a local immune cell infiltration in

human TGs. T cells positive for the CD3 and CD8 markers, and CD68-positive

macrophages were found in 30 of 42 examined TGs from 21 healthy individuals.

The presence of immune cells correlated constantly with the occurrence of

the HSV-1 latency-associated transcript (LAT) and only irregularly with the

presence of latent VZV protein. In contrast, uninfected TGs showed no immune

cell infiltration. Quantitative RT-PCR revealed that CD8, interferon-gamma,

tumor necrosis factor-alpha, IP-10, and RANTES transcripts were

significantly induced in TGs latently infected with HSV-1 but not in

uninfected TGs. The persisting lymphocytic cell infiltration and the

elevated CD8 and cytokine/chemokine expression in the TGs demonstrate for

the first time that latent herpesviral infection in humans is accompanied by

a chronic inflammatory process at an immunoprivileged site but without any

neuronal destruction. The chronic immune response seems to maintain viral

latency and influence viral reactivation.

Publication Types:

* Research Support, Non-U.S. Gov't

PMID: 14633592 [PubMed - indexed for MEDLINE]

12: J Immunol. 1996 Oct 15;157(8):3542-9.

Persistent cytokine expression in trigeminal ganglion latently infected

with herpes simplex virus type 1.

Halford WP, Gebhardt BM, Carr DJ. Department of Microbiology,

Louisiana State University Medical Center, New Orleans 70112, USA.

Following ocular infection, herpes simplex virus type 1 (HSV-1)

establishes latency in trigeminal ganglion (TG) neurons. Using reverse

transcription-PCR, cytokine gene expression was analyzed in the TGs of mice

infected with HSV-1. IL-2, TNF-alpha, IFN-gamma, IL-10, and RANTES mRNAs

were readily detected in TGs taken from mice 7 days postinoculation (PI).

Likewise, IL-2, IL-6, IL-10, and IFN-gamma protein were detected by ELISA of

TG homogenates. Between 5 and 45 days PI, IL-10, IFN-gamma, TNF-alpha, and

RANTES mRNAs were detected in nearly 100% of latently infected TGs (latent

infection was confirmed by reverse transcription-PCR detection of HSV-1

latency-associated transcripts). T cell-associated cytokine and chemokine

mRNAs (IL-2, IL-10, IFN-gamma, and RANTES) were still detected in the

majority of latently infected TG samples taken between 60 and 135 days PI.

In contrast, these cytokine mRNA species were rarely detected in uninfected

TGs. Measurement of serum Abs to HSV-1 at different times revealed that

anti-HSV-1 Ab concentrations approached a plateau in mice by 30 days PI but

remained at high levels 67 and 125 days PI. Although there was molecular

evidence of an ongoing immune response to HSV-1 in latently infected TG,

histologic analysis indicated that very few mononuclear cells remained in

the ganglion 60 days PI. Collectively, the results suggest that residual

lymphocytes encounter viral Ag during HSV-1 latency with sufficient

frequency to remain activated. The paradox of a persistent immune response

against a latent infection is discussed.

Publication Types: PMID: 8871654

------ End of Forwarded Message