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More MS news articles for October 2003

Regulatory functions of CD8+CD28- T cells in an autoimmune disease model

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J Clin Invest. 2003 Oct;112(7):1037-48
Najafian N, Chitnis T, Salama AD, Zhu B, Benou C, Yuan X, Clarkson MR, Sayegh MH, Khoury SJ.
77 Avenue Louis Pasteur, Room 714, Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA

CD8+ T cell depletion renders CD28-deficient mice susceptible to experimental autoimmune encephalomyelitis (EAE).

In addition, CD8-/-CD28-/- double-knockout mice are susceptible to EAE.

These findings suggest a role for CD8+ T cells in the resistance of CD28-deficient mice to disease.

Adoptive transfer of CD8+CD28- T cells into CD8-/- mice results in significant suppression of disease, while CD8+CD28+ T cells demonstrate no similar effect on the clinical course of EAE in the same recipients.

In vitro, CD8+CD28- but not CD8+CD28+ T cells suppress IFN-gamma production of myelin oligodendrocyte glycoprotein-specific CD4+ T cells.

This suppression requires cell-to-cell contact and is dependent on the presence of APCs.

APCs cocultured with CD8+CD28- T cells become less efficient in inducing a T cell-dependent immune response.

Such interaction prevents upregulation of costimulatory molecules by APCs, hence decreasing the delivery of these signals to CD4+ T cells.

These are the first data establishing that regulatory CD8+CD28- T cells occur in normal mice and play a critical role in disease resistance in CD28-/- animals.