Peripheral T-cell expansion and low infection rate after reduced-intensity conditioning and allogeneic blood stem cell transplantation

Abstract

Summary:Peripheral blood stem cell transplantation after reducedintensity conditioning (RIC-PBSCT) regimen is an alternative to conventional regimens with less immediate toxicity. Since immune recovery is of crucial importance for the control of infections, we retrospectively studied the recovery of T-, B-and NK cell subsets in 20 consecutive patients undergoing RIC-PBSCT. We also studied the thymic output using T-cell receptor excision circle assay. Engraftment was rapid and few infectious complications were seen: three early (before 2.5 months) cases of asymptomatic cytomegalovirus reactivation, two late Gram-negative bacterial infections and no fungal infection. While CD4 þ T-cell reconstitution was slow, CD8 þ T-cell counts were close to normal values at 4 months. Median CD19 þ B-cell counts reached normal values at 11 months. Rapid CD56 þ NK cell reconstitution was noticed as early as 1.5 months. Low T-cell receptor excision circle numbers and preponderance of memorytype subsets among T cells further suggested that CD8 þ T-cell reconstitution resulted predominantly from peripheral expansion and that thymic-dependent reconstitution was severely impaired. In conclusion, large peripheral Tcell expansion may compensate for late thymic-dependent lymphopoiesis, and may, with other factors such as NK and B-cell reconstitution and careful antiinfectious prophylaxis, help limit the incidence of severe infections after RIC-PBSCT. Bone Marrow Transplantation (2005) 35, 859-868.

CCL25 increases thymopoiesis after androgen withdrawal

“…In support of this hypothesis, emerging data also reveal that graft-versus-host disease is greater in the setting of impaired thymopoiesis. 2,[45][46][47] Studies also suggest that reduced intensity regimens may permit greater thymic renewal after transplant, 48,49 presumably as a result of TEC preservation. In addition to a selective loss of UEA ϩ TEC, our data suggest that renewal of thymopoiesis may be impaired because of diminished CCL25 production and inability to mediate ETP uptake and augment early DN development, restricting niche availability.…”

Prolonged CD4 T Cell Lymphopenia Increases Morbidity and Mortality after Renal Transplantation

“…The signal-joint TRECs were quantified in peripheral blood mononuclear cells using real-time quantitative PCR on LightCycler (Roche Diagnostics, Meylan, France), as described previously. 27 A series of standard dilutions of a plasmid containing the signal-joint breakpoint was used to quantify TRECs in each patient and control DNA sample. Cycle threshold was assessed using the second derivative method with the LightCycler 3.5.3 software (Roche Diagnostics).…”

MiHA Reactive CD4 and CD8 T-Cells Effect Resistance to Hematopoietic Engraftment Following Reduced Intensity Conditioning

“…Unfortunately, toxic affects together with the immunodeficiency early post-transplant has been associated with significant transplant related morbidity and mortality and therefore reduced intensity conditioning (RIC) regimens have been increasingly investigated [(5) reviewed in (6)(7)(8)(9)]. Experimental transplant models have demonstrated that RIC regimens ('mini' HCT) show promise in lowering the incidence of complications which arise following ablative conditioning, including infection and graft-versus-host disease (GVHD) (9)(10)(11)(12). However, control of graft rejection will remain a crucial factor in determining how 'mild' a level of immunosuppression can be administered which will continue to permit successful long-term engraftment.…”