Control of lymphocyte recirculation in man: I. Differential regulation of the peripheral lymph node homing receptor L-selectin on T cells during the virgin to memory cell transition

L. J. Picker, J. R. Treer, B. Ferguson-Darnell, P. A. Collins, D. Buck, L. W.M.M. Terstappen

Research output: Contribution to journalArticle

318 Scopus citations

Abstract

Conventional virgin lymphocytes of a given class show relatively homogeneous recirculation through secondary lymphoid tissues, whereas memory/effector populations are composed of distinct subsets with differential, often tissue-selective migratory capability. In keeping with these observations, CD45RA(high)/RO(low) 'virgin' T cells in human peripheral blood uniformly express the peripheral lymph node homing receptor (HR) L- selectin, whereas among the CD45RA(low)/RO(high) 'memory/effector' subset, the expression of this HR is bimodal. To investigate the mechanisms responsible for the generation of memory/effector T cell subsets with differential homing potential, we developed a multiparameter flow cytometric technique that defines a common pathway of post-thymic T cell differentiation in secondary lymphoid tissues. Our analyses indicate that the virgin to memory T cell transition is characterized by a stepwise, unidirectional progression through distinct CD45RA+/RO+ intermediates that allow the in vivo discrimination of early, middle, and late transitional T cells. In normal peripheral blood, few T cells with a transitional phenotype are identified, but in secondary lymphoid tissues, 2 to 10% of T cells have this phenotype, including those CD45RA+ T cells that 1) are morphologically blasts, 2) are in S or G2/M phase of the cell cycle, or 3) express activation Ag. General adhesion molecules (LFA-1, LFA-3, ICAM-1) are uniformly up-regulated concordant with changes in T cell expression of CD45RA/RO in all tissues examined. Early in the transition, L-selectin is also uniformly up-regulated, but in subsequent stages, T cell expression of this HR is preferentially down-regulated in mucosal lymphoid tissues, and retained in peripheral lymph node. Differential regulation of L-selectin can also be demonstrated in vitro by the activation of virgin T cells in the presence of specific cytokines - IL-2 induces L-selectin down-regulation, whereas IL-6 and particularly TGF-β1 promote L-selectin up-regulation. Taken together, these findings support the hypothesis that local microenvironments within particular secondary lymphoid tissues influence HR expression at the time of CD45RA/RO conversion, and thereby contribute to the formation of CD45RA(low)/RO(high) memory/effector T cell populations with tissue-selective homing behavior.

Original languageEnglish (US)
Pages (from-to)1105-1121
Number of pages17
JournalJournal of Immunology
Volume150
Issue number3
StatePublished - Jan 1 1993

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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