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Proliferation requirements of cytomegalovirus-specific, effector-type human CD8+ T cells

Ester M van Leeuwen1, Laila E Gamadia, Paul A Baars

  • 1Department of Internal Medicine, Divisions of Nephrology and Clinical Immunology and Rheumatology, Academic Medical Center, Meibergsreef 9, 1105 AZ Amsterdam, The Netherlands.

Journal of Immunology (Baltimore, Md. : 1950)
|November 8, 2002
PubMed

Insights

Cytomegalovirus (CMV)-specific CD45RA(+)CD27(-)CCR7(-) effector T cells, previously thought terminally differentiated, can proliferate upon stimulation. These cells also regain CCR7 and switch to CD45R0, contributing to adaptive immunity.

Area of Science:

  • Immunology
  • Virology
  • Cellular Biology

Background:

  • Latent viral infections involve distinct CD8(+) T cell subsets.
  • Effector-type CD45RA(+)CD27(-)CCR7(-) T cells were considered terminally differentiated with no proliferative capacity.

Purpose of the Study:

  • To investigate the proliferative potential of CMV-specific CD45RA(+)CD27(-)CCR7(-) T cells.
  • To determine if effector-type T cells can regain proliferative capacity and alter phenotype upon stimulation.

Main Methods:

  • Stimulation of CMV-specific CD45RA(+)CD27(-)CCR7(-) T cells with cognate peptide.
  • Co-stimulation with CD4(+) T cell help or cytokines (IL-2, IL-15, IL-21).
  • Analysis of cell surface phenotype (CD45RA, CD45R0, CCR7) and proliferative capacity.

Main Results:

  • Stimulation induced massive clonal expansion of CD45RA(+)CD27(-)CCR7(-) T cells.
  • These cells shifted phenotype from CD45RA to CD45R0 and re-expressed CCR7.
  • Effector functions were maintained throughout the process.

Conclusions:

  • CD45RA(+)CD27(-)CCR7(-) effector-type T cells are not terminally differentiated and possess proliferative capacity.
  • These cells can contribute to adaptive immunity by generating progeny during viral reactivation or reinfection.

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