Recovery of functional memory T cells in lung transplant recipients following induction therapy with alemtuzumab.
Profound T-cell depletion with the monoclonal antibody alemtuzumab facilitates reduced maintenance immunosuppression in abdominal and lung transplantation. While the phenotype of the post-depletional T cells has been characterized, little is known about their function. In the present study, global and CMV-specific T-cell function was assessed longitudinally in 23 lung transplant (LTx) recipients using T-cell assays (ImmuKnow and T Cell Memory, Cylex, Columbia, MD) during the first year posttransplant after induction therapy. Recovery of mitogen responses were seen at 2 weeks posttransplantation (65%PHA; 58% Con A), despite the low number of circulating T cells (<2%). These responses declined at 4-5 months (24%PHA; 54% Con A) and were partially reconstituted by 9 months (46% PHA; 73% Con A). CMV-specific responses recovered in 80% of R+ patients as early as 2 weeks posttransplant (n = 5) and 72% of patients had a memory response by 3 months (n = 11). In contrast, only 2 of 5 patients who did not exhibit memory responses pre-transplant (R-) developed transient CMV-specific T-cell responses. Our results show that profound depletion of T cells induced by alemtuzumab spares the functional subset of CMV-specific memory T cells. Conversely, CMV R- patients predepletion may require a prolonged period of prophylaxis.
Zeevi
A
A
Thomas E. Starzl Transplant Institute, University of Pittsburgh Medical Center, Division of Transplant Surgery, Pittsburgh, PA, USA. Zeevi@pitt.edu
Husain
S
S
Spichty
K J
KJ
Raza
K
K
Woodcock
J B
JB
Zaldonis
D
D
Carruth
L M
LM
Kowalski
R J
RJ
Britz
J A
JA
McCurry
K R
KR
D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D003208:Concanavalin A / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000209:etiology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D007165:Immunosuppression Therapy / Q000379:methods*; D008137:Longitudinal Studies; D016040:Lung Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000473:pathology*; D008212:Lymphocyte Depletion / Q000379:methods; D008934:Mitogens / Q000276:immunology; D010835:Phytohemagglutinins / Q000276:immunology; D012307:Risk Factors; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D008934:Mitogens; D010835:Phytohemagglutinins; D003208:Concanavalin A; D000074323:Alemtuzumab