Deregulated TCRαβ T cell population provokes extramedullary hematopoiesis in mice deficient in the common γ chain

Abstract Deficiency of the cytokine receptor common γ chain (γ c ) results in abnormal lymphoid development and a severe immunodeficiency disease due to the combined loss of the receptors for interleukins (IL)‐2, ‐4, ‐7, ‐9, and ‐15. We have observed the development of secondary hematopoiesis with circulating hematopoietic progenitor cells in adult mice harboring a null mutation in γ c . These extramedullary changes were not secondary to bone marrow failure or to an inability to maintain circulating blood counts. These results suggested that γ c ‐dependent cytokine signaling pathways modulate hematopoietic development. An intrinsic defect in γ c − hematopoietic stem cell committment appeared unlikely, as fetal liver hematopoiesis was unaltered in γ c − embryos. Furthermore, the absence of natural killer cells in γ c − mice was not responsible for the observed hematopoietic changes. Peripheral TCRαβ T cells from γ c − mice were characterized by an activated phenotype (CD62L lo , CD44 hi , CD69 hi ) and showed increased levels of transcripts for hematopoietic stimulating cytokines, including IL‐3 and granulocyte/macrophage‐colony‐stimulating factor. A predominance of these cells was detected in the bone marrow, suggesting a role for residual T cells in the enhanced hematopoiesis. Strikingly, the elimination of residual T cells from γ c − mice reduced splenic and circulating hematopoietic precursor frequencies to normal levels. These results clearly implicate a deregulated TCRαβ T cell population in the observed hematopoietic changes in γ c − mice, and emphasize the importance of γ c ‐dependent cytokine interactions in modulating mature T cell responses.