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Publication Detail
CMV promotes recipient T-cell immunity following reduced-intensity T-cell-depleted HSCT, significantly modulating chimerism status.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Sellar RS, Vargas FA, Henry JY, Verfuerth S, Charrot S, Beaton B, Chakraverty R, Quezada SA, Mackinnon S, Thomson KJ, Peggs KS
  • Publication date:
    22/01/2015
  • Pagination:
    731, 739
  • Journal:
    Blood
  • Volume:
    125
  • Issue:
    4
  • Status:
    Published
  • Country:
    United States
  • PII:
    S0006-4971(20)39514-8
  • Language:
    eng
  • Keywords:
    Allografts, Cytomegalovirus, Cytomegalovirus Infections, Female, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Humans, Immunity, Cellular, Lymphocyte Depletion, Male, Transplantation Chimera
Abstract
Cytomegalovirus (CMV) remains a significant cause of morbidity after allogeneic hematopoietic stem cell transplantation (HSCT). Clinical risk varies according to a number of factors, including recipient/donor CMV serostatus. Current dogma suggests risk is greatest in seropositive recipient (R+)/seronegative donor (D-) transplants and is exacerbated by T-cell depletion. We hypothesized that in the setting of reduced-intensity T-cell-depleted conditioning, recipient-derived CMV-specific T cells escaping deletion may contribute significantly to CMV-specific immunity and might therefore also influence chimerism status. We evaluated 105 recipients of alemtuzumab-based reduced-intensity HSCT and collated details on CMV infection episodes and T-cell chimerism. We used CMV-specific HLA multimers to enumerate CMV-specific T-cell numbers and select cells to assess chimerism status in a subset of R+/D- and R+/seropositive donor patients. We show that in R+/D- patients, CMV-specific T cells are exclusively of recipient origin, can protect against recurrent CMV infections, and significantly influence the chimerism status toward recipients. The major findings were replicated in a separate validation cohort. T-cell depletion in the R+/D- setting may actually, therefore, foster more rapid reconstitution of protective antiviral immunity by reducing graft-vs-host directed alloreactivity and the associated elimination of the recipient T-cell compartment. Finally, conversion to donor chimerism after donor lymphocytes is associated with clinically occult transition to donor-derived immunity.
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Research Department of Haematology
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