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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.

Abstract：

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. CONCLUSION: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.

journal_name

Exp Hematol

journal_title

Experimental hematology

authors

Yakoub-Agha I,Saule P,Depil S,Grutzmacher C,Boulanger F,Magro L,Jouet JP,Dessaint JP,Labalette M

doi

10.1016/j.exphem.2007.03.006

subject

Has Abstract

pub_date

2007-06-01 00:00:00

pages

861-71

issue

eissn

0301-472X

issn

1873-2399

pii

S0301-472X(07)00187-7

journal_volume

pub_type

临床试验,杂志文章

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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.