PIM1 reconstitutes thymus cellularity in interleukin 7- and common gamma chain-mutant mice and permits thymocyte maturation in Rag- but not CD3gamma-deficient mice.
The majority of lymphomas induced in Rag-deficient mice by Moloney murine leukemia virus (MoMuLV) infection express the CD4 and/or CD8 markers, indicating that proviral insertions cause activation of genes affecting the development from CD4(-)8(-) pro-T cells into CD4(+)8(+) pre-T cells. Similar to MoMuLV wild-type tumors, 50% of CD4(+)8(+) Rag-deficient tumors carry a provirus near the Pim1 protooncogene. To study the function of PIM proteins in T cell development in a more controlled setting, a Pim1 transgene was crossed into mice deficient in either cytokine or T cell receptor (TCR) signal transduction pathways. Pim1 reconstitutes thymic cellularity in interleukin (IL)-7- and common gamma chain-deficient mice. In Pim1-transgenic Rag-deficient mice but notably not in CD3gamma-deficient mice, we observed slow expansion of the CD4(+)8(+) thymic compartment to almost normal size. Based on these results, we propose that PIM1 functions as an efficient effector of the IL-7 pathway, thereby enabling Rag-deficient pro-T cells to bypass the pre-TCR-controlled checkpoint in T cell development.
Jacobs
H
H
Basel Institute for Immunology, CH-4005 Basel, Switzerland. Jacobs@BIL.CH
Krimpenfort
P
P
Haks
M
M
Allen
J
J
Blom
B
B
Démollière
C
C
Kruisbeek
A
A
Spits
H
H
Berns
A
A
D000818:Animals; D017252:CD3 Complex / Q000235:genetics* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000276:immunology; D005434:Flow Cytometry; D007142:Immunoglobulin gamma-Chains / Q000235:genetics* / Q000276:immunology; D015851:Interleukin-7 / Q000235:genetics* / Q000276:immunology; D016399:Lymphoma, T-Cell / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008979:Moloney murine leukemia virus / Q000235:genetics / Q000276:immunology; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051573:Proto-Oncogene Proteins c-pim-1; D013601:T-Lymphocytes / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology
D017252:CD3 Complex; D004268:DNA-Binding Proteins; D007142:Immunoglobulin gamma-Chains; D015851:Interleukin-7; D011518:Proto-Oncogene Proteins; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; C496636:Pim1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1