PF766 T CELL EXHAUSTION PROFILE (CD4+/CD28/PER+/GRA+ CD8+/CD28/PER+/GRA+) IN STEM CELL TRANSPLANTATION, CMV RE ACTIVATIONS AND RESPIRATORY VIRUS INFECTION.CELLULAR DYNAMICS IN THE FIRST 100 DAYS POST SCT
Authors: Villanueva M. , Figuera A. , Perez Y. , Cuellar C. , Lopez P. , Galvan J.M. , De La Cámara R. , García‐Noblejas A. , Cardeñoso L. , Munoz C. 
Published: June 2019

Background:

Recipients of allogeneic stem cells grafts have clonally expanded CD8+/CD28‐ T lymphocytes during the early period after SCT, this cellular dynamic is associated with the acquisition of a cytoxic phenotype. This scenario predisposes to continuous inflammation. On the other hand, respiratory viruses (RV) are recognized as the predominant leading to pneumonia after SCT, and CMV re activations were associated with morbi‐mortality in SCT patients.RVI and CMV re‐activations might contribute to the emergence of exhausted T cells phenotype.

Aims:

The present study aimed to evaluate the dynamics of T cell exhaustion profile during the +100d after SCT(auto, allo/patients with RVI and CMV re activations)

Methods:

Informed consent was obtained from all patients. PBs were obtained previous SCT and at day+100 post SCT from 37 patients (11 auto, 26 allo). To evaluate the expression of CD4+/CD28Per+/Gran+, CD8+/CD28Per+/Gran+. Flow cytometry analysis was performed: 100 μL of PB was labeled, with a panel of 8 AbMos: PERFORIN FITC, GRANZIME PE, CD4PerCP, CD28 APC, CD8 APCH7, CD16/56 V450 and CD45 V500. The molecular detection of RV was tested with theCLART® Pneumovir assay (Clinical Array Technology, Genomica, Spain). CMV detection was performed by quantitative CMV PCR (COBAS®Amplicor® CMV MonitorTM test) (qPCR CT). Statistical analysis was performed with IBM SPSS v24

Results:

Thirty seven patients were evaluated from November 2016 to December 2017 at the University Hospital of La Princesa, Madrid Spain. Patient characteristics:Table 1.The median percentages of baseline CD8+/CD28‐ cell line was 8,81%(range, 0,6–49,5) and the median percentages of CD8+/CD28‐ cellline at +100d were 29,2%(range, 1,2–60,8).Likewise, significant differences were found(p = 0.001).The group of patients who had an RVI and the group without RVI: in the CD8+/CD28+100d cell line, the median percentages of the RVI patients were 58.43%(range, 42.7–68.4)and the median percentages in the uninfected were 29.26%(range, 13.2–38.9)(p = 0.002). CMV re activations,the median percentages at +100d of CD8+/CD28‐ cell line with CMV‐ was 5,7%(range, 0,6–20,6)and the median percentage of CD8+/CD28‐with CMV+ at +100d was 36,7%(range, 13,5–68,7)p = 0,001.CMV reactivations and RVI, the median percentages at +100d of CD8+/CD28‐cell line with CMV/RVI was 6,82%(range, 0,6–20,6)and the medianpercentage of CD8+/CD28‐ with CMV+/RVI+ at +100d was 34,6%(range, 1,4–49,8)p = 0,012.

Summary/Conclusion:

We show a dynamic change of the T cell exhausted phenotype CD8+/CD28‐throughout the SCT, an also ID interactions (RVI, CMV re activations).There is a statistically significant difference when analyzing patients with RVI+ vs RVI‐ (baseline vs +100d), also might exist a synergic effect RVI+/CMV+.The CD8+/CD28‐Tcell population has been shown to contain virus specific memory CTL that respond to CMV and to other antigens.Thus, clonally expanded CD8+CD28‐ Tcells following STC may be derived from the T cells recognizing antigens that persistently exist in the host (CMV) or to the exposure to certain virus antigens in the first 100d after STC (synergic effect), this may contribute to the appearance of populations of exhausted T cells CD8+/CD28‐ favoring an inflammatory environment and triggering certain immunological complications (immunedysregulation).We need to follow up these patients and correlate with other clinical epidemiological variables in SCT(aGVHD,cGVHD,pulmonary functional tests,ID complications)

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