CD8+ T-cell selection, function, and death in the primary immune response in vivo
Margaret F.C. Callan, … , Chris Hatton, Andrew J. McMichael
Margaret F.C. Callan, … , Chris Hatton, Andrew J. McMichael
Published November 15, 2000
Citation Information: J Clin Invest. 2000;106(10):1251-1261. https://doi.org/10.1172/JCI10590.
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Article

CD8+ T-cell selection, function, and death in the primary immune response in vivo

Abstract

The primary immune response to Epstein Barr virus (EBV) is characterized by striking proliferation of EBV-specific CD8+ T cells. In this study we have investigated the clonal composition and functional properties of the cells mediating this primary response and have analyzed the mechanisms that control the downregulation of the primary response and the selection of memory cells. We show that massively expanded T-cell clones often dominate the primary antigen-specific T-cell response. Despite the enormous extent of expansion, the virus-specific T cells express high levels of intracellular perforin and are potently cytotoxic. They are, however, functionally heterogeneous in their ability to secrete proinflammatory cytokines, with subpopulations of the antigen-specific T cells being hyporesponsive. The primary response is closely regulated, and the majority of cells are programmed to die via a cytokine-rescuable pathway, leaving only small populations of memory T cells surviving. Comparison of the clonal composition of primary and memory responses in vivo shows that the clones that dominate the primary response are relatively heavily culled during the downregulation of the primary response and the establishment of T-cell memory.

Authors

Margaret F.C. Callan, Chrysoula Fazou, Hongbing Yang, Tim Rostron, Kathryn Poon, Chris Hatton, Andrew J. McMichael

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Figure 2

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The TCR repertoire of CD8+ T cells specific for EBV antigens during the ...
The TCR repertoire of CD8+ T cells specific for EBV antigens during the primary and memory immune responses. PBMCs taken from donor NS52 (a), donor NS60 (b), donor NS33 (c), and donor NS60 (d), during primary EBV infection (black bars) and 1 year later (hatched bars), were stained with a panel of TCR V region–specific mAb’s, with the B8/RAKFKQLL tetrameric complex (a and b), or with the A2/GLCTLVAML tetrameric complex (c and d), and with an Ab specific for CD8. The TCR V–region use of CD8+ T cells reacting with the relevant tetrameric complex is shown. The frequency (% of CD8+ T cells) of RAKFKQLL-specific T cells during primary infection and 1 year later in donor NS52 was 40.2% and 4.4%, respectively, and in donor NS60 was 33% and 4.3%, respectively. The frequency of GLCTLVAML-specific T cells during primary infection and 1 year later in donor NS33 was 11% and 5.5%, respectively, and in donor NS60 was 6.6% and 1.3%, respectively.