Maternal microchimerism leads to the presence of interleukin-2 in interleukin-2 knock out mice: implications for the role of interleukin-2 in thymic function.
The role of interleukin-2 (IL-2) in thymic development is uncertain. Not surprisingly, IL-2 knockout (KO) mice have been used to address this question. However, as we report here, such mice are chimeric, containing both IL-2 KO cells and IL-2-expressing cells transferred in utero from their heterozygous mothers. These cells produce IL-2 in amounts detectable by conventional means, and their presence in lymphoid tissues confounds efforts to define the true IL-2 KO phenotype. To minimize the amount of IL-2 available to the thymus, we subjected recombinase activating gene-1 KO mice to bone marrow transplantation using IL-2 KO donors, and then followed the reconstitution of the thymus. The thymuses of these mice became increasingly aberrant over time, including abnormalities in both stromal cells and thymocytes. These results demonstrate that IL-2 is critical to several aspects of thymic function, a finding previously obscured by the presence of IL-2 in IL-2 KO mice.
Wrenshall
Lucile E
LE
Division of Transplantation, University of Nebraska Medical Center, 983285 Nebraska Medical Center, Omaha, NE 68198-3285, USA. lwrenshall@unmc.edu
Stevens
Elliot T
ET
Smith
Deandra R
DR
Miller
John D
JD
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D046528:Chimerism; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000235:genetics / Q000502:physiology*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D008431:Maternal-Fetal Exchange / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009928:Organ Specificity; D010766:Phosphorylation; D011247:Pregnancy; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology* / Q000473:pathology
D018398:Homeodomain Proteins; D007376:Interleukin-2; C064658:RAG-1 protein; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)