Integrin functions play a key role in the differentiation of thymocytes in vivo.
T cells express a variety of surface proteins as they develop to maturity in the thymus. In addition to the TCR-CD3 complex and the two major coreceptors, CD4 and CD8, other surface proteins expressed include receptors for cytokines, growth factors, counterreceptors, and extracellular matrix molecules. To determine the role of integrin adhesion receptors in T cell development, we have expressed a trans-dominant inhibitor of integrin function in the thymus. This inhibitor leads to a block of adhesion to fibronectin due to reduced activation of integrin receptors. This reduced adhesion leads to a partial block in differentiation from CD4-CD8- cells to CD4+CD8+ cells, after the CD25+ stage, suggesting that integrins are important during Lck-mediated differentiation. Furthermore, the overall production of CD4+ cells is reduced compared with that of CD8+ cells without changes in negative selection, suggesting that integrins may be involved in the determination of the fate of the cell as well. These results demonstrate that integrin receptor function is required for proper thymocyte development in vivo.
Schmeissner
P J
PJ
Department of Pathology, Columbia University College of Physicians and Surgeons, Black Building 1422, 630 West 168th Street, New York, NY 10032, USA.
Xie
H
H
Smilenov
L B
LB
Shu
F
F
Marcantonio
E E
EE
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002448:Cell Adhesion; D002454:Cell Differentiation; D002478:Cells, Cultured; D018628:Gene Dosage; D019012:Integrin beta1 / Q000235:genetics / Q000502:physiology; D016023:Integrins / Q000037:antagonists & inhibitors / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000145:classification; D013950:Thymus Gland / Q000196:embryology / Q000254:growth & development / Q000276:immunology*
D019012:Integrin beta1; D016023:Integrins; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins