POSTER

1 – Laboratoire

d’Immunochimie, INSERM U548/CEA, Grenoble, France. 2 – Don C. Gnocchi Foundation,

Milan, Italy. 3 – Hopital Henri Mondor, Créteil, France. 4 – BioMérieux, Marcy

l’étoile, France.

The presence of MSRV, a retroviral

element defining a novel family of human endogenous retroviruses (HERV-W) has

now been confirmed in serum and CSF of patients with multiple sclerosis (MS) and

a correlation between circulating MSRV

Understanding immuno-pathogenic

potential of such retroviral expression in humans thus became critical. We have

recently found that MSRV and its envelope (MSRV-ENV) protein displayed

superantigen (Sag) properties associated with the production of pro-inflammatory

cytokines. The potent immunopathogenicity and the pro-inflammatory properties of

MSRV virions were later confirmed in vivo in SCID mice grafted with human

peripheral blood mononuclear cells

(PBMC). Given the extreme pro-inflammatory features observed in this animal

model, the objectives of the present study were to characterize the

pro-inflammatory effects of a recombinant MSRV protein (MSRVprot). The effects

of MSRVprot were first studied in vitro on human PBMC and were characterized by

the production of TNF-a,

IL-1b

and IL-6, three cytokines mainly produced by activated antigen presenting cells

(APC). IFN-g,

a T cell cytokine was not or only slightly secreted in response to this protein,

thus demonstrating its ability to preferentially activate APCs rather than T

lymphocytes. The specificity of these

results was then demonstrated by the neutralization of the cytokine production

In an attempt to link the potential effects of

this protein with MS disease, MSRVprot pro-inflammatory properties were then

further evaluated in PBMC of MS patients and compared with healthy controls. No

differences were found between both groups for the expression of the T cell

marker CD69 and the production of IFN-g.

However, when we looked at the secretion of APC derived cytokines, we observed

that MSRVprot mediated IL-6

production was increased in MS patients while

TNF-a

and IL-1b

remained unchanged. Interestingly, this over IL-6 production was later found to

Elevated

levels of IL-6 in plasma, CSF and CNS tissue of MS patients have been reported

in several publications, and a role for this cytokine has been argued in

Altogether our data demonstrate

that a new MSRV protein preferentially targets and activates cells of the innate

immune system such as monocytes and macrophages rather than T lymphocytes and

induces the over secretion of IL-6 in MS.

These properties could thus further demonstrate