Selective expression of integrin alpha 4 beta 7 on a subset of human CD4+ memory T cells with Hallmarks of gut-trophism.
Human memory CD4+ T lymphocytes are heterogenous in expression of integrins; one subset has the unexpected phenotype beta 1 low alpha 4 high. We demonstrate that this subset is unique among CD4+ cells in expression of high levels of alpha 4 beta 7, detected by a distinctive mAb Act-1. alpha 4 beta 7 is involved in binding to both fibronectin and vascular cell adhesion molecule-1; Act-1 blocks cell binding to the former and augments binding to the latter. Act-1 expression marks a subset of memory cells that, unlike the predominant circulating memory cell, has up-regulated beta 7 rather than beta 1. Their phenotype is distinct from that described for skin-homing T cells and is fully consistent with that described for gut-homing T cells. Differential adhesion capacity of this subset is verified by selective binding to FN and vascular cell adhesion molecule-1 in a beta 1-independent fashion. Thus, alpha 4 beta 7 detected on this subset of circulating normal T cells fits the expectations for a gut-homing receptor.
Schweighoffer
T
T
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Tanaka
Y
Y
Tidswell
M
M
Erle
D J
DJ
Horgan
K J
KJ
Luce
G E
GE
Lazarovits
A I
AI
Buck
D
D
Shaw
S
S
D000911:Antibodies, Monoclonal / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000502:physiology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology; D002478:Cells, Cultured; D005353:Fibronectins / Q000502:physiology; D006801:Humans; D007156:Immunologic Memory; D016023:Integrins / Q000032:analysis*; D007422:Intestines / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000502:physiology*; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D005353:Fibronectins; D016023:Integrins; D019010:Vascular Cell Adhesion Molecule-1