Activated alpha4 integrins are preferentially expressed on immature thymocytes and activated T cells.

Fengyu Shu,Frank Seibold,David Erle,John F Kearney,Bernhard Holzmann

doi:10.1080/1044667021000024229

Abstract

We have identified a novel mAb, SG31, which recognizes the mouse integrin α4 subunit. Unlike the epitopes recognized by other anti-α4 antibodies, the SG31 epitope is expressed on subpopulations of thymocytes and peripheral T cells. After manganese ion, but not phorbol myristic acetate activation, the epitope is induced and expressed on the majority of peripheral T cells. These data suggest that the SG31 epitope is an activation epitope and that manganese ions activate α4 integrins by inducing a conformational change. Comparative flow cytometric analyses showed that the SG31 epitope as well as the epitope detected by other anti-α4 antibodies is expressed on all B lineage cells. In the T lineage, expression of the α4 integrins is down-regulated during thymocyte development. Although mature thymocytes still express the α4 integrins, they lose almost entirely the activation epitope recognized by SG31. In contrast, the most immature thymocytes express high levels of this epitope. In the periphery, SG31 epitope is expressed mostly by activated T cells, in contrast to the overall population of T cells that express the α4 integrins at homogenous levels. These results suggest that the activation of the α4 integrins is parallel to that of T cells.

Highlights

The a4 integrin a4b7 and a4b1 are heterodimeric cell surface adhesion molecules involved in leukocyte cell – cell and cell – matrix interactions and migration (Elices, 1994). a4b1 is distributed on essentially all hemopoietic lineage precursors and most mature blood cells except erythrocytes, platelets and neutrophils (Elices, 1994; Lobb and Hemler, 1994). a4b1 expression can be induced on activated neutrophils (Reinhardt et al, 1996) and upregulated during T and B cell activation (Hemler, 1990; Postigo et al, 1991)
Since integrins are the only known leukocyte antigens consisting of heterodimers with similar molecular weight, our initial data suggest that SG31 may react with a4b1 or aLb2 because of their comparable distribution on leukocytes
The major findings of this report are that: (i) mAb SG31 recognizes the mouse integrin a4 subunit, (ii) most T cells express a4 integrins but not the SG31 epitope, which is in contrast to B cells all of which express the SG31 epitope, (iii) SG31 epitope is up-regulated on T cells by Mnþþ, (iv) primarily immature thymocytes and activated T cells express SG31 epitope, (v) PMA-activated splenic T cells up-regulate a4 integrins and SG31 epitope, and (vi) cells expressing high levels of a4 integrins express high levels of SG31 epitope

Summary

Introduction

The a4 integrin a4b7 and a4b1 are heterodimeric cell surface adhesion molecules involved in leukocyte cell – cell and cell – matrix interactions and migration (Elices, 1994). a4b1 is distributed on essentially all hemopoietic lineage precursors and most mature blood cells except erythrocytes, platelets and neutrophils (Elices, 1994; Lobb and Hemler, 1994). a4b1 expression can be induced on activated neutrophils (Reinhardt et al, 1996) and upregulated during T and B cell activation (Hemler, 1990; Postigo et al, 1991). A4b1 expression can be induced on activated neutrophils (Reinhardt et al, 1996) and upregulated during T and B cell activation (Hemler, 1990; Postigo et al, 1991). It is expressed on non-lymphoid tissues in developing embryos (Stepp et al, 1994; Sheppard et al, 1994) and various nonhematopoietic tumor cells (Lobb and Hemler, 1994). The ligands for a4b1 are the alternatively spliced connecting segment-1 (CS1) region of extracellular matrix protein fibronectin and domains 1 and 4 of vascular cell adhesion molecule-1 (VCAM-1, CD106) (Elices, 1994). The a4 subunit itself may function as a ligand for a4b1 and a4b7 (Altevogt et al, 1995)

Methods

Results

Conclusion