The number of circulating recent thymic emigrants is severely reduced 1 year after a single dose of alemtuzumab in renal transplant recipients

Abstract

Summary To better understand the kinetics of the delayed reconstitution of peripheral CD4+ T‐cells after depletion with a single administration of alemtuzumab (AL) for renal transplantation, we evaluated in these patients the percentage and absolute number of recent thymic emigrants (RTEs) CD4+ T cells, together with naive and memory subsets, defined by the analysis of CD31, CD45RA and CCR7 expression, and compared with patients treated with a nondepleting protocol based on basiliximab, and with healthy controls. In AL‐treated patients, the number of circulating CD4+ T cells was greatly reduced 1 year after the infusion (P < 0.01), but the proportions of central memory, effector memory and terminally differentiated effector memory subsets among CD4+ cells were significantly increased. On the contrary, the proportion and the absolute number of naïve CD4+ T cells, although progressively increasing with time, were severely reduced. In particular, the absolute number of RTEs had only very slight increase with time (P = 0.049) and was dramatically low 1 year after the therapy (P < 0.01 vs. healthy controls; P < 0.05 vs. basiliximab‐treated transplant recipients). These data suggest that a prolonged defective thymic output after AL therapy in renal transplant recipients is one of the main causes of the persistent CD4+ T‐cell lymphopenia observed in these patients.

Differential Reconstitution of T Cell Subsets following Immunodepleting Treatment with Alemtuzumab (Anti-CD52 Monoclonal Antibody) in Patients with Relapsing–Remitting Multiple Sclerosis

“…Whereas alemtuzumab efficiently depletes all CD52 + cells, the delayed reconstitution of CD4 + cells, resulting from deficient CD4 + cell homeostatic proliferation, susceptibility to apoptosis (28), and a relative expansion of immunoregulatory (29), which is even more prominent in MS patients (30), may also contribute to the prolonged CD4 + cell decrease and to the resetting of long-term CD4 + cell counts to numbers that are lower than at baseline (31).…”

Immune Monitoring of Kidney Recipients: Biomarkers to Appreciate Immunosuppression -Associated Complications

“…This renders difficult to interpret the effects of thymic activity in the context of lymphopenia. In contrast, Scarsi et al (2010) reported a massive reduction of RTE one year post-transplantation after Campath-1H administration. This supports that naive CD4 + T cells −including RTE− may be highly sensitive to ATG (Louis et al, 2007;Gurkan et al, 2010)(see also below, paragraph §2.1.2) and that time is necessary for RTE "replenishment" after T cell depletion.…”

“…Whether data obtained with ATG can be transposed to Alemtuzumab remains to be determined. Nevertheless, few clinical studies are available regarding the CD4 + T cell lymphopenia induced by Alemtuzumab administration (Scarsi et al, 2010) not always in the context of kidney transplantation (Cox et al, 2005).…”

CD4 T Lymphopenia, Thymic Function, Homeostatic Proliferation and Late Complications Associated with Kidney Transplantation

“…This renders difficult to interpret the role of thymic activity in the context of lymphopenia. In contrast, Scarsi et al [47] reported a massive reduction of RTE one year post-transplantation after Campath-1H/Alemtuzumab administration. Prolonged selective CD4 + T cell lymphopenia suggests that naive CD4 + T cells −including RTE− are highly sensitive to ATG [31,75] and that time is necessary for RTE "replenishment" after T cell depletion.…”

“…We imagine that these biomarkers identified in the setting of ATG can be transposed to other depleting therapies, such as Campath-1H/ Alemtuzumab. Indeed, clinical studies are available regarding the prolonged CD4 + T cell Current Issues and Future Direction in Kidney Transplantationlymphopenia induced by Alemtuzumab administration [47], not always in the context of kidney transplantation [48,49].…”