High level of perforin expression in T cells: An early prognostic marker of the severity of herpesvirus reactivation after allogeneic stem cell transplantation in adults.
BACKGROUND
Epstein-Barr virus (EBV) and cytomegalovirus reactivations are frequent complications of hematopoeitic allogeneic stem cell transplantation (SCT) because of a lack of T cell control after immunosuppression. Early diagnosis of reactivation and subsequent preemptive therapy relies on frequent viral load measurement. Additional virus-specific T cell reconstitution data could improve the predictive value of viral load detection for viral complications after transplantation. Here, we studied perforin expression in CD8(+) T cells as a measure of cytotoxic T cell capacity in relation to the occurrence of viral reactivation.


METHODS
In a prospective study, we monitored 40 patients during the first 3 months after transplantation and measured viral loads in combination with intracellular perforin expression in CD8(+) T cells.


RESULTS
Median perforin expression in CD8(+) T cells throughout follow-up was higher in patients with viral reactivations than in patients without viral reactivations (4.9% vs 2.3%; P = .001). The median percentage of perforin-expressing CD8(+) T cells in patients with high viral reactivations exceeding 1000 copies/mL (10.7%) was statistically significantly higher than that in patients with minor reactivations of 50-1000 copies (4.0%), that in patients with detectable EBV loads that did not exceed the detection limit of 50 copies/mL (2.9%), and that in patients without reactivations (0.8%). Patients with high viral reactivations reached a high percentage of perforin-expressing CD8(+) T cells (>10.2%) more often and faster than did patients with low viral loads (1000 copies/mL) or without viral reactivations. High perforin expression preceded high viral loads.


CONCLUSIONS
Perforin-expressing CD8(+) T cells may be useful as an easy-to-measure prognostic marker for identifying patients at risk for severe viral reactivation very soon after SCT.
Pietersma
F L
FL
Department of Immunology, University Medical Center Utrecht, the Netherlands.
van Dorp
S
S
Jacobi
R
R
Ran
L
L
Nanlohy
N M
NM
Schuurman
R
R
Minnema
M C
MC
Meijer
E
E
van Baarle
D
D
D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000175:diagnosis / Q000276:immunology*; D020031:Epstein-Barr Virus Infections / Q000175:diagnosis / Q000276:immunology*; D005260:Female; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D054353:Perforin / Q000096:biosynthesis*; D011379:Prognosis; D012189:Retrospective Studies; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D014775:Virus Activation / Q000276:immunology*; D055815:Young Adult
D054353:Perforin