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© The Rockefeller University Press, 0022-1007/1999/10/1059/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 8, October 18, 1999 1059-1068

PIM1 Reconstitutes Thymus Cellularity in Interleukin 7– and Common {gamma} Chain–Mutant Mice and Permits Thymocyte Maturation in Rag- but Not CD3{gamma}-deficient Mice

Heinz Jacobsa, Paul Krimpenfortb, Mariëlle Haksc, John Allenb, Bianca Blomc, Corinne Démollièrea, Ada Kruisbeekc, Hergen Spitsc, and Anton Bernsb
a Basel Institute for Immunology, CH-4005 Basel, Switzerland
b Division of Molecular Genetics and Centre of Biomedical Genetics, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
c Division of Immunology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands

Correspondence to: Heinz Jacobs, Basel Institute for Immunology, Grenzacherstr. 487, CH-4005 Basel, Switzerland. Tel:41-61-605-1281 Fax:41-61-605-1364 E-mail:Jacobs{at}BII.CH.

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 CD3{gamma}-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.

Key Words: common {gamma} chain, IL-7, Rag, proviral tagging, lymphomagenesis, pre-T cell development


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