The number of circulating recent thymic emigrants is severely reduced 1 year after a single dose of alemtuzumab in renal transplant recipients.
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.
Scarsi
Mirko
M
Rheumatology and Clinical Immunology, and Nephrology, Spedali Civili, Brescia, Italy.
Bossini
Nicola
N
Malacarne
Fabio
F
Valerio
Francesca
F
Sandrini
Silvio
S
Airò
Paolo
P
D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000077552:Basiliximab; D015415:Biomarkers / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects* / Q000276:immunology; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D016030:Kidney Transplantation / Q000276:immunology*; D047589:Leukocyte Reduction Procedures / Q000379:methods; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000187:drug effects
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D015415:Biomarkers; D007166:Immunosuppressive Agents; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011993:Recombinant Fusion Proteins; D000074323:Alemtuzumab; D000077552:Basiliximab