Document 0420 DOCN M9550420 TI Differential expression of integrins alpha 6 and alpha 4 determines pathways in human peripheral CD4+ T cell differentiation. DT 9505 AU Schweighoffer T; Luce GE; Tanaka Y; Shaw S; Experimental Immunology Branch, National Cancer Institute,; National Institutes of Health, Bethesda, MD 20892. SO Cell Adhes Commun. 1994 Oct;2(5):403-15. Unique Identifier : AIDSLINE MED/95144469 AB Integrins mediate leukocyte adhesion to vascular endothelium and thereby influence leukocyte recirculation. We have explored expression by peripheral blood T cells of beta 1 and beta 7 integrins, particularly alpha 4 beta 1 (VLA-4, CD49d), alpha 4 beta 7 (LPAM-1) and alpha 6 beta 1 (VLA-6, CD49f). Integrin expression differs between CD4+ cells and CD8+ cells in that CD4+ cells 1) are more heterogeneous, particularly for alpha 4; 2) express on the average less alpha 4 and beta 7; and 3) express on the average more alpha 6 and beta 1. 2D gel electrophoretic analysis was combined with flow cytometric analysis to determine which integrin chain pairs are expressed by the CD45RO- (naive) and CD45RO+ (memory) subsets of CD4+ cells. CD45RO- (naive) cells express homogeneously at intermediate levels the three integrin pairs alpha 6 beta 1, alpha 4 beta 1 and alpha 4 beta 7. Although 2D gel analysis suggests similar average integrin chain composition for CD45RO+CD4+ (memory) cells, flow cytometric analysis demonstrates multiple subsets of CD45RO+ cells differing markedly from each other and from naive cells in levels of expression of alpha 6 and alpha 4 integrins. There are a minimum of three CD45RO+ subsets: 1) alpha 4 beta 1hi alpha 6 beta 1hi alpha 4 beta 7neg, which comprises the majority of memory cells; 2) alpha 4 beta 7hi alpha 6 beta 1low presumptive gut-homing memory cells; and 3) alpha 6 beta 1hi alpha 4 beta 7neg alpha 4 beta 1neg, a previously unidentified subset expected to have unique migrational-functional properties. Of particular importance in these results are: the expression by CD4+ naive cells of alpha 6 beta 1, alpha 4 beta 1 and alpha 4 beta 7, the overall prominence and regulation of alpha 6 beta 1 on CD4+ cells, and the selective decreases as well as increases in alpha 4 beta 7 and alpha 4 beta 1 during CD4+ memory specialization. Taken together, these results suggest that differential regulation of expression of alpha 4 and alpha 6 integrin chains that accompany naive-to-memory transition in CD4+ cells are instrumental in generating functional subsets of CD4+ memory cells with specialized recirculation abilities. DE Cell Differentiation Comparative Study CD4-Positive T-Lymphocytes/CYTOLOGY/*IMMUNOLOGY CD8-Positive T-Lymphocytes/CYTOLOGY/IMMUNOLOGY Electrophoresis, Gel, Two-Dimensional Flow Cytometry Gene Expression Human Integrins/ANALYSIS/*BIOSYNTHESIS/ISOLATION & PURIF Support, U.S. Gov't, P.H.S. T-Lymphocyte Subsets/CYTOLOGY/IMMUNOLOGY T-Lymphocytes/CYTOLOGY/*IMMUNOLOGY JOURNAL ARTICLE SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).