The role of the integrin LFA-1 in T-lymphocyte migration.

Abstract:

:A successful immune response depends on the migration of lymphocytes into lymph nodes or inflamed tissues where they make contact with antigen-presenting cells. We are interested in how one member of the integrin family, leukocyte function-associated antigen-1 (LFA-1), controls the function and, in particular, the migration of immune cells. We find that this integrin operates not only as an adhesion receptor for T lymphoblasts (T cells) but also induces their migration in vitro at approximately 15 microm/min. Migration requires active myosin light chain kinase at the leading edge and Rho kinase at the trailing edge of the cell. Two active conformations of LFA-1 are differently distributed on the T-cell membrane and regulate independent aspects of migration. High-affinity LFA-1 is located in a midcell 'focal zone' and influences the speed of migration, whereas intermediate affinity LFA-1 controls leading edge adhesions. Manipulating LFA-1 conformation in vivo can be performed, for example, by creating the active conformation in a transgenic mouse, and this model gives further insight into the role of LFA-1 in migration. In humans, the beneficial effect of functioning CD18 integrins in combating infections in vivo is illustrated by rare patients displaying two forms of leukocyte adhesion deficiency. In summary, we speculate that T cells have evolved a mode of rapid migration that is of paramount importance in achieving the high-speed immune surveillance upon which depends the body's protection against diverse invaders from pathogens to cancer cells.

journal_name

Immunol Rev

journal_title

Immunological reviews

authors

Smith A,Stanley P,Jones K,Svensson L,McDowall A,Hogg N

doi

10.1111/j.1600-065X.2007.00537.x

subject

Has Abstract

pub_date

2007-08-01 00:00:00

pages

135-46

eissn

0105-2896

issn

1600-065X

pii

IMR537

journal_volume

218

pub_type

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