[HTML][HTML] Regulatory functions of CD8+CD28 T cells in an autoimmune disease model

N Najafian, T Chitnis, AD Salama, B Zhu… - The Journal of …, 2003 - Am Soc Clin Investig
N Najafian, T Chitnis, AD Salama, B Zhu, C Benou, X Yuan, MR Clarkson, MH Sayegh
The Journal of clinical investigation, 2003Am Soc Clin Investig
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+ …
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-γ 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.
The Journal of Clinical Investigation