Regulatory functions of CD8+CD28– T cells in an autoimmune disease model
Nader Najafian, … , Mohamed H. Sayegh, Samia J. Khoury
Nader Najafian, … , Mohamed H. Sayegh, Samia J. Khoury
Published October 1, 2003
Citation Information: J Clin Invest. 2003;112(7):1037-1048. https://doi.org/10.1172/JCI17935.
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Article Autoimmunity

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

Abstract

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.

Authors

Nader Najafian, Tanuja Chitnis, Alan D. Salama, Bing Zhu, Christina Benou, Xueli Yuan, Michael R. Clarkson, Mohamed H. Sayegh, Samia J. Khoury

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Figure 1

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Screening of CD28–/–CD8–/– mice by flow cytometry and PCR. A representat...
Screening of CD28–/–CD8–/– mice by flow cytometry and PCR. A representative example of screening of CD28–/–CD8–/– mice and WT mice is shown. Cells were stained and analyzed by FACS for expression of CD8 and CD28. For the PCR screening, genomic DNA was extracted from tails of animals. In the CD8 PCR sample, homozygous samples produced a single 343-bp band, and WT mice produced a single 265-bp band. Heterozygotes produced both bands. In the CD28 PCR sample, homozygous samples produced a single 740-bp band, and WT mice produced a single 600-bp band. Heterozygous mice produced both bands. All PCR experiments included a no-template control and control reactions using DNA from known heterozygous and WT samples. Neg, negative; FL1-H, fluorescence channel 1.