       Document 0900
 DOCN  M9650900
 TI    Migration pathways of CD4 T cell subsets in vivo: the CD45RC- subset
       enters the thymus via alpha 4 integrin-VCAM-1 interaction.
 DT    9605
 AU    Bell EB; Sparshott SM; Ager A; Immunology Research Group, University of
       Manchester, UK.
 SO    Int Immunol. 1995 Nov;7(11):1861-71. Unique Identifier : AIDSLINE
       MED/96162444
 AB    The present investigation examines the localization and migration of
       purified T cell subsets in comparison with B cells, CD8 T cells and CD4+
       CD8- single-positive thymocytes. CD4 T cell subsets in the rat are
       defined by mAb MRC OX22 (anti-CD45RC), which distinguishes resting CD4 T
       cells (CD45RC+) from those (CD45RC-) which have encountered antigen in
       the recent past--subpopulations often referred to as 'naive' and
       'memory'. Purified, 51Cr-labelled CD45RC+ CD4 T cells broadly reflected
       the migration pattern of CD8 T cells and B cells. Early localization to
       the spleen was followed by a redistribution to mesenteric lymph nodes
       (MLN) and cervical lymph nodes (CLN), B cells migrating at a slightly
       slower tempo. There was almost no localization of these subpopulations
       to the small or large intestine [Peyer's patches (PP) excluded]. In
       contrast, CD45RC- CD4 T cells (indistinguishable in size from the
       CD45RC+ subset) localized in large numbers to the intestine; they were
       present here at the earliest time point (0.5 h), persisted for at least
       48 h but did not accumulate, indicating a rapid exit. Numerically,
       localization of CD45RC- CD4 T cells in the MLN could be accounted for
       entirely by afferent drainage from the intestine. Unexpectedly, CD45RC-
       CD4 T cells (but not other subsets) localized and accumulated in the
       thymus. In vivo treatment with mAb HP2/1 against the integrin alpha 4
       subunit inhibited almost entirely CD45RC- CD4 T cell migration into the
       PP (98.1%), intestine (87.1%), MLN (89.1%) and thymus (93.5%); migration
       into the CLN was only reduced by half. To distinguish between
       recognition of MAdCAM-1 and VCAM-1 by alpha 4-containing integrins,
       recipients were treated with mAb 5F10 against rat VCAM-1. Except for the
       thymus and a small reduction in CLN, localization of CD45RC- CD4 T cells
       was unaffected; entry to the thymus was almost completely blocked
       (92.3%) by anti-VCAM-1. The results indicated (i) that CD45RC- CD4 T
       cells alone showed enhanced localization to the gut and PP, probably via
       alpha 4 beta 7-MAdCAM-1 interaction; (ii) that many CD45RC- cells
       entered non-mucosal LN independently of alpha 4 integrin or VCAM-1; and
       (iii) that entry of mature recirculating CD45RC- CD4 T cells into the
       thymus across thymic endothelium was apparently regulated by alpha 4
       integrin-VCAM-1 interaction.
 DE    Animal  Antigens, CD/*METABOLISM  Antigens, CD45/*IMMUNOLOGY
       B-Lymphocytes/IMMUNOLOGY  Cell Adhesion Molecules/PHYSIOLOGY  Cell
       Movement/*IMMUNOLOGY  CD4-Positive
       T-Lymphocytes/*CLASSIFICATION/*IMMUNOLOGY/  TRANSPLANTATION
       CD8-Positive T-Lymphocytes/IMMUNOLOGY  Female  Male  Rats  Rats, Inbred
       Strains  Rats, Nude  Support, Non-U.S. Gov't  Thymus Gland/*IMMUNOLOGY
       Vascular Cell Adhesion Molecule-1/*METABOLISM  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

