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More MS news articles for November 2002

Susceptibility to Theiler's murine encephalomyelitis virus-induced demyelinating disease in BALB/cAnNCr mice is related to absence of a CD4+ T-cell subset

http://www.ingenta.com/isis/searching/ExpandTOC/ingenta?issue=infobike://arn/ms/2002/00000008/00000006&index=5

Multiple Sclerosis, 1 October 2002, vol. 8, no. 6, pp. 469-474(6)
Karls K.A.[1]; Denton P.W.[1]; Melvold R.W.[1]
[1] Department of Microbiology and Immunology, School of Medicine and Health Sciences, University of North Dakota, 501 North Columbia Road, Grand Forks, North Dakota 58202, USA

Two histocompatible substrains of BALB/c mice (BALB/cByJ, BALB/cAnNCr) are resistant and susceptible, respectively, to Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) a model for viral etiology of human multiple sclerosis.

BALB/cByJ mice become susceptible following low-dose irradiation given prior to infection.

Resistance is restored by adoptive transfer of CD8+ (but not CD4+) splenic T cells from infected, unirradiated BALB/cByJ donors.

In contrast, resistance is conferred to BALB/cAnNCr mice by adoptive transfer of either CD4+ or CD8+ T cells from resistant BALB/cByJ donors.

T cells from BALB/cAnNCr mice cannot confer protection.

To integrate these two observations, we hypothesized that the BALB/cAnNCr mice possess precursors of the regulatory CD8+ T cells, but fail to activate them because they lack a critical CD4+ T-cell subpopulation.

We tested this model using serial transfers.

The transfer of CD4+ T cells from the BALB/cByJ to the BALB/cAnNCr mice permitted development of BALB/cAnNCr CD8+ T cells that, in turn, provided resistance when transferred into susceptible recipients.

The BALB/cByJ CD4+ T cells, which activated the CD8+ cells, were sensitive to low-dose irradiation, unlike CD4+ T cells involved in the later inflammatory demyelination.

Thus, susceptibility of BALB/cAnNCr mice is due to a defective/absent CD4+ T-cell subset acting immediately after infection.