Recovery of varicella-zoster virus-specific T cell immunity after T cell-depleted allogeneic transplantation requires symptomatic virus reactivation.

Reactivated varicella-zoster virus (VZV) infection causes herpes zoster and commonly occurs after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Because VZV-specific T cell immunity is essential to prevent virus reactivation, we developed an interferon-gamma enzyme-linked immunosorbent spot (ELISPOT) assay for the sensitive detection of VZV-reactive T cells at the single-cell level ex vivo. We used this assay to monitor the frequency of VZV-reactive T cells in 17 seropositive patients during the first year after T cell-depleted allo-HSCT. The patients did not receive anti-herpesvirus prophylaxis after stem cell engraftment. Independent of the magnitude of transferred donor immunity, VZV-reactive T cell numbers decreased to low levels (median, 2/mL; range, 0 to 35/mL) in peripheral blood early after transplantation. Only patients with subsequent zoster (n = 5) exhibited a dramatic boost in VZV-reactive T cells (median, 366/mL; range, 158 to 756/mL), which was induced by the reactivation event. The postzoster VZV-reactive T cell levels were similar to those seen in healthy virus carriers. In contrast, antiviral T cell levels remained low in patients without VZV disease. Our results demonstrate that VZV-specific T cell immunity recovered efficiently during zoster in T cell-depleted allo-HSCT recipients. It did not reconstitute spontaneously in nonzoster patients, even in the absence of antiviral prophylaxis. Prospective studies should investigate whether VZV vaccination can substitute for natural resensitization by virus disease.