Hematopoietic Stem Cell Functional Failure in Interleukin-2-Deficient Mice

Abstract

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.