T Cell Developmental Defects in 'Viable Motheaten' Mice Deficient in SHP-1 Protein-Tyrosine Phosphatase. Developmental Defects are Corrected in vitro in the Presence of Normal Hematopoietic-Origin Stromal Cells and in vivo by Exogenous IL-7.
Document Type
Article
Publication Date
2002
First Page
119
Last Page
130
JAX Source
J Autoimmun 2002 Mar; 18(2):119-30.
Abstract
Defects in the gene that encodes SHP-1 protein tyrosine phosphatase result in multiple hematopoietic abnormalities and generalized autoimmunity in viable motheaten (me(v)) mice. These mice also exhibit early thymic involution and abnormalities in T cell development. Here, we describe the use of fetal thymic organ culture (FTOC) and bone marrow adoptive transfer to study the effects of SHP-1 deficiency on thymocyte development. Chimeric FTOC established with normal bone marrow placed onto deoxyguanosine-treated fetal thymic lobes or onto scid fetal thymic lobes generated T cells. Bone marrow from SHP-1-deficient me(v)/ me(v) mice generated decreased numbers of T cells in chimeric FTOC established using deoxyguanosine-treated thymi but generated normal numbers in chimeric FTOC established using scid thymi. However, scid fetal thymi seeded with me(v)/ me(v) bone marrow also exhibited morphological abnormalities and contained elevated numbers of macrophages. Addition of IL-7 to me(v)/ me(v) bone marrow-seeded scid FTOC led to increased cell numbers, particularly of macrophages. Intrathymic injection of IL-7 partially restored the ability of progenitor cells in me(v)/ me(v) bone marrow to populate the thymus of adoptive recipients. We conclude that abnormal T cell development in me(v)/ me(v) mice may in part be due to defects in the ability of bone marrow-derived accessory cells to provide bioavailable IL-7 to developing thymocytes. Copyright 2002 Elsevier Science Ltd.
Recommended Citation
Christianson SW,
Greiner DL,
Deluca D,
Leif J,
Phillips NE,
Hayes SM,
Hayashi S,
Joliat MJ,
Lyons BL,
Shultz LD.
T Cell Developmental Defects in 'Viable Motheaten' Mice Deficient in SHP-1 Protein-Tyrosine Phosphatase. Developmental Defects are Corrected in vitro in the Presence of Normal Hematopoietic-Origin Stromal Cells and in vivo by
Exogenous IL-7. J Autoimmun 2002 Mar; 18(2):119-30.