Immune reconstitution following rabbit antithymocyte globulin.
Depletional induction therapies are routinely used to prevent acute rejection and improve transplant outcome. The effects of depleting agents on T-cell subsets and subsequent T-cell reconstitution are incompletely defined. We used flow cytometry to examine the effects of rabbit antithymocyte globulin (rATG) on the peripheral T-cell repertoire of pediatric and adult renal transplant recipients. We found that while rATG effectively depleted CD45RA+CD27+ naïve and CD45RO+CD27+ central memory CD4+ T cells, it had little effect on CD45RO+CD27- CD4+ effector memory or CD45RA+CD31-, CD45RO+CD27+ and CD45RO+CD27- CD8+ T cell subsets. When we performed a kinetic analysis of CD31+ recent thymic emigrants and CD45RA+/RO+ T cells, we found evidence for both thymopoiesis and homeostatic proliferation contributing to immune reconstitution. We additionally examined the impact of rATG on peripheral CD4+Foxp3+ T cells. We found that in adults, administration of rATG-induced peripheral expansion and new thymic emigration of T cells with a Treg phenotype, while CD4+Foxp3+ T cells of thymic origin predominated in children, providing the first evidence that rATG induces Treg in vivo. Collectively our data indicate that rATG alters the balance of regulatory to memory effector T cells posttransplant, providing an explanation for how it positively impacts transplant outcome.
Gurkan
S
S
Division of Pediatric Nephrology, UMDNJ, NJ.
Luan
Y
Y
Division of Nephrology, Mount Sinai School of Medicine, NY.
Dhillon
N
N
Division of Nephrology, Mount Sinai School of Medicine, NY.
Allam
S R
SR
Division of Nephrology, Mount Sinai School of Medicine, NY.
Montague
T
T
Recanati Miller Transplantation Institute, Mount Sinai School of Medicine, NY.|Division of Nephrology, Brown University Medical School, RI.
Bromberg
J S
JS
Department of Gene and Cell Medicine, Mount Sinai School of Medicine, NY.|Department of Surgery, Mount Sinai School of Medicine, NY.|Recanati Miller Transplantation Institute, Mount Sinai School of Medicine, NY.
Ames
S
S
Department of Surgery, Mount Sinai School of Medicine, NY.|Recanati Miller Transplantation Institute, Mount Sinai School of Medicine, NY.
Lerner
S
S
Department of Surgery, Mount Sinai School of Medicine, NY.|Recanati Miller Transplantation Institute, Mount Sinai School of Medicine, NY.
Ebcioglu
Z
Z
Recanati Miller Transplantation Institute, Mount Sinai School of Medicine, NY.|Division of Nephrology, Mount Sinai School of Medicine, NY.
Nair
V
V
Recanati Miller Transplantation Institute, Mount Sinai School of Medicine, NY.|Division of Nephrology, Mount Sinai School of Medicine, NY.
Dinavahi
R
R
Recanati Miller Transplantation Institute, Mount Sinai School of Medicine, NY.|Division of Nephrology, Mount Sinai School of Medicine, NY.
Sehgal
V
V
Recanati Miller Transplantation Institute, Mount Sinai School of Medicine, NY.|Division of Nephrology, Mount Sinai School of Medicine, NY.
Heeger
P
P
Recanati Miller Transplantation Institute, Mount Sinai School of Medicine, NY.|Division of Nephrology, Mount Sinai School of Medicine, NY.
Schroppel
B
B
Recanati Miller Transplantation Institute, Mount Sinai School of Medicine, NY.|Division of Nephrology, Mount Sinai School of Medicine, NY.
Murphy
B
B
Recanati Miller Transplantation Institute, Mount Sinai School of Medicine, NY.|Division of Nephrology, Mount Sinai School of Medicine, NY.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D002452:Cell Count; D002648:Child; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D007155:Immunologic Factors / Q000627:therapeutic use*; D007156:Immunologic Memory / Q000187:drug effects; D007674:Kidney Diseases / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011817:Rabbits; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism
D000961:Antilymphocyte Serum; C499816:FOXR2 protein, human; D051858:Forkhead Transcription Factors; D007155:Immunologic Factors