PMID- 12590705 OWN - NLM STAT- MEDLINE DCOM- 20031106 LR - 20071114 IS - 1525-8165 (Print) IS - 1525-8165 (Linking) VI - 11 IP - 6 DP - 2002 Dec TI - Hematopoietic stem cell functional failure in interleukin-2-deficient mice. PG - 905-12 AB - The effects of interleukin-2 (IL-2) deficiency on hematopoiesis were tested by measuring cellular compositions in peripheral blood, spleen, thymus, and bone marrow of 3- to 5-month-old gene-targeted Il2 null (Il2(-/-)) mice using the Advia 120 Hematology system and fluorescence-activated cell staining (FACS). Il2(-/-) mice developed hematological failure and autoimmune responses, showing variable but significant degrees of anemia, lymphocytopenia, thrombocytopenia, splenomegaly, thymus involution, and weight loss. Surprisingly, Il2(-/-) mice had normal numbers of bone marrow cells (BMCs) with increased numbers of Lin(-)Kit(+)Sca1(+)CD34(-) and Lin(-)Kit(+)Sca1(+)CD34(+) cells that are normally associated with hematopoietic stem cells (HSCs) and progenitor cells. Day-12 colony-forming units-spleen cells were slightly reduced in Il2(-/-) mice. When Il2(-/-) and Il2(+/+) mice were compared for long-term HSC function in vivo in the competitive repopulation assay, BMCs from Il2(-/-) donors had 10- to 20-fold less HSC repopulating ability, which affected both myeloid and lymphoid cell lineages. Thus, HSCs from Il2(-/-) mice can proliferate normally but are functionally defective for reconstituting lethally irradiated recipients. FAU - Chen, J AU - Chen J AD - Hematology Branch, National Heart, Lung and Blood Institute, Bethesda, MD 20892-1652, USA. chenji@nhlbi.nih.gov FAU - Astle, C M AU - Astle CM FAU - Harrison, D E AU - Harrison DE LA - eng GR - CA 34196/CA/NCI NIH HHS/United States GR - R01 HL 58820/HL/NHLBI NIH HHS/United States GR - R01 HL 63230/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Hematother Stem Cell Res JT - Journal of hematotherapy & stem cell research JID - 100892915 RN - 0 (Interleukin-2) SB - IM MH - Animals MH - Autoimmunity MH - Blood Cells/cytology MH - Bone Marrow Cells/immunology MH - Cell Count MH - Flow Cytometry MH - Hematopoiesis MH - Hematopoietic Stem Cells/pathology/*physiology MH - Immunophenotyping MH - Interleukin-2/*deficiency/genetics MH - Mice MH - Mice, Knockout MH - Phenotype MH - Spleen/cytology MH - Thymus Gland/cytology EDAT- 2003/02/20 04:00 MHDA- 2003/11/07 05:00 CRDT- 2003/02/20 04:00 PHST- 2003/02/20 04:00 [pubmed] PHST- 2003/11/07 05:00 [medline] PHST- 2003/02/20 04:00 [entrez] AID - 10.1089/152581602321080565 [doi] PST - ppublish SO - J Hematother Stem Cell Res. 2002 Dec;11(6):905-12. doi: 10.1089/152581602321080565.