cytomegalovirus promotes expansion of pre- existing t-cell immunity following allogeneic...
TRANSCRIPT
Cytomegalovirus promotes expansion of pre-existing T-cell immunity following allogeneic transplantation significantly modulating chimerism status
Rob S. Sellar, Frederick Arce Vargas, Jake Y. Henry, Stephanie Verfuerth, Sarah Charrot, Sergio A. Quezada, Stephen Mackinnon, Kirsty J. Thomson,
and Karl S. Peggs*
University College London Cancer Institute
The Dogma
• CMV reactivations are increased if you T-deplete• Highest risk population R+/D-• New therapeutic strategies are needed
What if it is wrong?
What if it is wrong?
CMV reactivations
What if it is wrong?
CMV reactivations Days of treatment
Problematic CMV reactivations are associated with low levels of recipient chimerism
CMV reactivations
Problematic CMV reactivations are associated with low levels of recipient chimerism
CMV reactivations Days of treatment
Problematic CMV reactivations are restricted to patients with significant GvHD
CMV reactivations
Problematic CMV reactivations are restricted to patients with significant GvHD
CMV reactivations Days of treatment
Patients with significant GvHD had lower absolute lymphocyte counts
CMV appears to influence levels of recipient chimerism
CMV appears to influence levels of recipient chimerism
CMV appears to influence levels of recipient chimerism
CMV influences chimerism even in the absence of GvHD
Streptamer positive cells are exclusively of recipient origin
Streptamer positive cells are exclusively of recipient origin
Donor
Recipient
CD4+
CD8+ Strep-
CD8+ Strep+
Patient 1 Patient 2 Patient 3
DLI can be followed by a primary immune response to CMV
Donor
Recipient
Pre-DLI
4 weeks
8 weeks
12 weeks
18 weeks
CD8+ Strep- CD8+ Strep+ CD4+
Conclusions
• recipient-derived virus-specific T cells that have escaped deletion during non-myeloablative conditioning can protect against recurrent CMV infection
• expansion of these cells post transplant has a significant influence on levels of recipient chimerism
• “Campath Paradox” - T cell-depletion in the R+D- setting may paradoxically foster more rapid reconstitution of protective antiviral immunity by reducing graft-versus-host directed alloreactivity and the associated elimination of the recipient T cell compartment
Acknowledgements
• UCL Cancer Institute• Tumour Immunogy Group– Dr Karl S Peggs
– Dr Sergio A Quesada
– Dr Frederick Arce Vargas
– Jake Y Henry
• Royal Free Hospital – Professor Stephen Mackinnon
– Stephanie Verfuerth
• UCLH – Dr Kirsty Thomson
– Dr Sarah Charrot