PMID- 19775313 OWN - NLM STAT- MEDLINE DCOM- 20091230 LR - 20230124 IS - 1600-6143 (Electronic) IS - 1600-6135 (Linking) VI - 9 IP - 11 DP - 2009 Nov TI - Memory T-cell predominance following T-cell depletional therapy derives from homeostatic expansion of naive T cells. PG - 2615-23 LID - 10.1111/j.1600-6143.2009.02820.x [doi] AB - 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. FAU - Sener, A AU - Sener A AD - Division of Transplantation, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA. FAU - Tang, A L AU - Tang AL FAU - Farber, D L AU - Farber DL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090922 PL - United States TA - Am J Transplant JT - American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons JID - 100968638 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antilymphocyte Serum) RN - 0 (Isoantigens) RN - D7RD81HE4W (thymoglobulin) SB - IM MH - Animals MH - Antibodies, Monoclonal/immunology/pharmacology MH - Antilymphocyte Serum MH - CD4 Lymphocyte Count MH - CD4-Positive T-Lymphocytes/*cytology/*immunology MH - Cell Division/immunology MH - Homeostasis/immunology MH - Immunologic Memory/*immunology MH - Immunophenotyping MH - Isoantigens/immunology MH - *Leukocyte Reduction Procedures MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - *Transplantation Immunology EDAT- 2009/09/25 06:00 MHDA- 2009/12/31 06:00 CRDT- 2009/09/25 06:00 PHST- 2009/09/25 06:00 [entrez] PHST- 2009/09/25 06:00 [pubmed] PHST- 2009/12/31 06:00 [medline] AID - S1600-6135(22)01889-5 [pii] AID - 10.1111/j.1600-6143.2009.02820.x [doi] PST - ppublish SO - Am J Transplant. 2009 Nov;9(11):2615-23. doi: 10.1111/j.1600-6143.2009.02820.x. Epub 2009 Sep 22.