Memory T-cell predominance following T-cell depletional therapy derives from homeostatic expansion of naive T cells.
Am J Transplant
; 9(11): 2615-23, 2009 Nov.
Article
em En
| MEDLINE
| ID: mdl-19775313
T-cell depletion reportedly leads to alterations in the T-cell compartment with predominant survival of memory phenotype CD4 T cells. Here, we asked whether the prevalence of memory T cells postdepletion results from their inherent resistance to depletion and/or to the homeostatic expansion of naive T cells and their phenotypic conversion to memory, which is known to occur in lymphopenic conditions. Using a 'mosaic memory' mouse model with trackable populations of alloreactive memory T cells, we found that treatment with murine antithymocyte globulin (mATG) or antilymphocyte serum (ALS) effectively depleted alloreactive memory CD4 T cells, followed by rapid homeostatic proliferation of endogenous CD4 T cells peaking at 4 days postdepletion, with no homeostatic advantage to the antigen-specific memory population. Interestingly, naive (CD44lo) CD4 T cells exhibited the greatest increase in homeostatic proliferation following mATG treatment, divided more extensively compared to memory (CD44hi) CD4 T cells and converted to a memory phenotype. Our results provide novel evidence that memory CD4 T cells are susceptible to lymphodepletion and that the postdepletional T-cell compartment is repopulated to a significant extent by homeostatically expanded naive T cells in a mouse model, with important important implications for immune alterations triggered by induction therapy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Imunologia de Transplantes
/
Linfócitos T CD4-Positivos
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Procedimentos de Redução de Leucócitos
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Memória Imunológica
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Am J Transplant
Ano de publicação:
2009
Tipo de documento:
Article