Dynamics of gd T Cell Expansion Can Predict the Resolution of CMV Infection and the Emergence of a Mutant Viral Strain in Kidney Transplant Recipients.

Abstract

Cytomegalovirus (CMV) infection in solid organ transplantation is associated with increased morbidity and mortality, particularly in the case of the emergence of a CMV mutant strain with anti-viral drug resistance. In this situation, immune monitoring assays should provide relevant clinical information on efficient CMV-specific T cells response. For many years, we have shown that gd T lymphocytes (gd-TL) are involved in the control of CMV infection. The purpose of this study was to assess if gd-TL kinetics can predict the resolution of CMV infection in high risk patients: D+ R- and R+ with anti-thymocyte globulin - ATG, or the emergence of a mutant strain. Methods gd-TL kinetics has been described in D+ R- or R+/ATG kidney transplant recipients between 2003 and 2011. This kinetics was compared between infected and non infected patients and between patients with and without mutation. gd-TL expansion was estimated by a linear mixed model, the time of expansion was defined as the date of occurrence of this expansion from the beginning of infection. Results 167 patients D+ R- (93 infected and 74 non-infected) and 104 R+/ATG (74 infected and 30 non-infected) patients were included. The gd-TL expansion following CMV infection was comparable in D+R- and R+/ATG patients. Time of gd-TL expansion was highly correlated with the duration of DNAemia (r=0.91, p < 0.0001). The delay of gd-TL expansion was closely associated with the presence of a mutant strain (p < 0.0007). This mutation was predicted by persistent DNAemia after 39 days of gd-TL expansion (AUC= 0.76). Conclusion In high risk patients, gd-TL expansion is related to the resolution of CMV infection. Conversely, the delay of expansion and the persistence of DNAemia after expansion are predictive of the occurrence of a mutant strain. Monitoring gd-TL could be useful during CMV infection in order to predict the resolution of the infection and the emergence of a mutant viral strain.