Advertisement

CMV-specific CD8+ T-cell function is not impaired in chronic lymphocytic leukemia

G. Doreen te Raa, Maria Fernanda Pascutti, Juan J. García-Vallejo, Emilie Reinen, Ester B. M. Remmerswaal, Ineke J. M. ten Berge, René A. W. van Lier, Eric Eldering, Marinus H. J. van Oers, Sanne H. Tonino and Arnon P. Kater

Key Points

  • Expression of exhaustion markers is decreased on CMV-specific CD8+ T cells from CLL patients as compared with those from age-matched HCs.

  • Functionality of CMV-specific CD8+ T cells in CLL with respect to cytokine production, cytotoxicity, and immune synapse formation is preserved.

Abstract

In chronic lymphocytic leukemia (CLL), CD8+ T cells exhibit features of exhaustion and impaired functionality. Yet, reactivations of latent viruses such as cytomegalovirus (CMV) are uncommon in untreated CLL, suggesting that antiviral responses are uncompromised. We analyzed phenotypical and functional characteristics of CMV-specific CD8+ T cells in CLL patients in comparison with age-matched healthy controls (HCs). Despite increased expression of the inhibitory receptors PD1, CD160, and CD244 on total CD8+ T cells in CLL, expression levels of these markers were decreased on CMV-tetramer+CD8+ T cells. Second, cytokine production upon stimulation with both phorbol 12-myristate 13-acetate/ionomycin and CMV-peptide–loaded antigen-presenting cells was intact in CMV-tetramer+CD8+ T cells. Third, CMV-tetramer+CD8+ T cells of CLL patients and HCs were equally effective in killing CMV-peptide–loaded target cells. Finally, quantitative imaging flow cytometry revealed that the proportion of CD8+ T cells forming immunologic synapses with CMV-peptide–loaded B cells was intact. In conclusion, despite evidence for global T-cell dysfunction in CLL, we show here that CLL-derived CMV-specific CD8+ T cells display lower expression of exhaustion markers and are functionally intact. These data indicate that the changes in the T-cell compartment in CLL may be more heterogeneous than presently assumed.

  • Submitted August 30, 2013.
  • Accepted November 10, 2013.
View Full Text