       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).

