Comparative analysis of naïve and memory CD4+ and CD8+ T-cell subsets in bone marrow and G-CSF-mobilized peripheral blood stem cell allografts: impact of donor characteristics.
OBJECTIVE
Donor T cells expressing lymph node homing receptors are the foremost initiators of acute graft-vs-host disease (aGVHD), and a high proportion of CD4(+)CCR7(+) T cells in human leukocyte antigen-matched allografts has been shown to confer a high risk of aGVHD without interfering in other outcomes.


METHODS
Naïve, central memory (T(CM)), effector memory (T(EM)), and terminally differentiated effector memory (T(TD)) subsets, further subdivided by CD28 expression, were compared in 52 bone marrow and 37 granulocyte colony-stimulating factor-mobilized peripheral blood harvests.


RESULTS
CCR7(+) cells (naïve and T(CM)) predominated in the CD4(+) population, whereas CD8(+) memory cells were chiefly CCR7(neg) in the grafts. Donor age, antecedent of chronic infections, and graft type were independent factors influencing graft composition. CD8(+) naïve cells negatively correlated and CD8(+) T(EM) positively correlated with age. Cytomegalovirus seropositivity was associated with more CD8(+) T(TD) and diminished CD28 expression. Toxoplasmosis seropositivity was associated with more CD4(+) T(CM) (p = 0.021). Marrow grafts comprised more CD28(+) cells within CD8(+) T(TD), but the percentage of CD4(+)CCR7(+) cells did not differ significantly between the two graft sources. Each of the four CD4(+) subsets and the percentage of CD4(+)CCR7(+) cells (p < 0.001) were correlated between graft and venous blood analyzed in 42 donors before harvest procedures.


CONCLUSIONS
This study provides reference values for CD4(+) and CD8(+) naïve and memory subsets within allografts applicable to the healthy donor population and indicates that beforehand analysis of a whole-blood sample can help evaluating the risk of aGVHD conferred by each donor and, when possible, choosing the one conferring the lowest risk.
Yakoub-Agha
Ibrahim
I
Service des Maladies du Sang, CHU, Lille, France. i-yakoub-agha@chru-lille.fr
Saule
Pasquine
P
Depil
Stephane
S
Grutzmacher
Claudine
C
Boulanger
Florence
F
Magro
Leonardo
L
Jouet
Jean-Pierre
JP
Dessaint
Jean-Paul
JP
Labalette
Myriam
M
D000208:Acute Disease; D000328:Adult; D018106:CD28 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology*; D046148:Donor Selection; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D007156:Immunologic Memory; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000276:immunology; D014184:Transplantation, Homologous
C515370:CCR7 protein, human; D018106:CD28 Antigens; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D016179:Granulocyte Colony-Stimulating Factor