Memory T-cell predominance following T-cell depletional therapy derives from homeostatic expansion of naive T cells.
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.
Division of Transplantation, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
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Sener
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Tang
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Farber
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000961:Antilymphocyte Serum; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D006706:Homeostasis / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D016130:Immunophenotyping; D007519:Isoantigens / Q000276:immunology; D047589:Leukocyte Reduction Procedures; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014181:Transplantation Immunology
D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D007519:Isoantigens; C512542:thymoglobulin