Regulatory functions of CD8+CD28- T cells in an autoimmune disease model.
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.
Najafian
Nader
N
Brigham and Women's Hospital, Boston, Massachusetts, USA.
Chitnis
Tanuja
T
Salama
Alan D
AD
Zhu
Bing
B
Benou
Christina
C
Yuan
Xueli
X
Clarkson
Michael R
MR
Sayegh
Mohamed H
MH
Khoury
Samia J
SJ
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000502:physiology; D018106:CD28 Antigens / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D016212:Transforming Growth Factor beta / Q000502:physiology
D018106:CD28 Antigens; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma