Longitudinal assessment of T cell inhibitory receptors in liver transplant recipients and their association with posttransplant infections.
Am J Transplant
; 18(2): 351-363, 2018 02.
Article
in En
| MEDLINE
| ID: mdl-29068155
ABSTRACT
Current immunosuppression regimens in organ transplantation primarily inhibit T cells. However, T cells are also critical in protective immunity, especially in immune-compromised patients. In this study, we examined the association of T cell dysfunction, as marked by expression of T cell exhaustion molecules, and posttransplant infections in a cohort of liver transplant patients. We focused on Programmed Death 1 (PD-1) and T cell Ig- and mucin-domain molecule 3 (Tim-3), which are potent co-inhibitory receptors, and their persistent expression often leads to T cell dysfunction and compromised protective immunity. We found that patients with the highest expression of PD-1 +Tim-3+ T cells in the memory compartment before transplantation had increased incidence of infections after liver transplantation, especially within the first 90 days. Longitudinal analysis in the first year showed a strong association between variability of PD-1 and Tim-3 expression by T cells and infectious episodes in transplant patients. Furthermore, T cells that expressed PD-1 and Tim-3 had a significantly reduced capacity in producing interferon (IFN)-γ in vitro, and this reduced IFN-γ production could be partially reversed by blocking PD-1 and Tim-3. Interestingly, the percentage of Foxp3+ regulatory T cells in liver transplant patients was stable in the study period. We concluded that the functional status of T cells before and after liver transplantation, as shown by PD-1 and Tim-3 expression, may be valuable in prognosis and management of posttransplant infections.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Postoperative Complications
/
Liver Transplantation
/
Programmed Cell Death 1 Receptor
/
Hepatitis A Virus Cellular Receptor 2
/
Immunologic Memory
/
Infections
Type of study:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Am J Transplant
Journal subject:
TRANSPLANTE
Year:
2018
Document type:
Article
Affiliation country:
United States