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

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

Research output: Contribution to journalArticle

313 Citations (Scopus)

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 - 1993
Externally publishedYes

Fingerprint

Lymphocyte Homing Receptors
L-Selectin
Lymphocytes
T-Lymphocytes
Lymphoid Tissue
CD58 Antigens
Homing Behavior
Phenotype
G2 Phase
T-Lymphocyte Subsets
Intercellular Adhesion Molecule-1
Cell Division
Population
Interleukin-2
Cell Differentiation
Interleukin-6
Cell Cycle
Mucous Membrane

ASJC Scopus subject areas

  • Immunology

Cite this

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

In: Journal of Immunology, Vol. 150, No. 3, 1993, p. 1105-1121.

Research output: Contribution to journalArticle

@article{52176ed7f233489492c058a3a2b8e67d,
title = "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",
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.",
author = "Louis Picker and Treer, {J. R.} and B. Ferguson-Darnell and Collins, {P. A.} and D. Buck and Terstappen, {L. W M M}",
year = "1993",
language = "English (US)",
volume = "150",
pages = "1105--1121",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "3",

}

TY - JOUR

T1 - Control of lymphocyte recirculation in man

T2 - I. Differential regulation of the peripheral lymph node homing receptor L-selectin on T cells during the virgin to memory cell transition

AU - Picker, Louis

AU - Treer, J. R.

AU - Ferguson-Darnell, B.

AU - Collins, P. A.

AU - Buck, D.

AU - Terstappen, L. W M M

PY - 1993

Y1 - 1993

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0027262235&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027262235&partnerID=8YFLogxK

M3 - Article

VL - 150

SP - 1105

EP - 1121

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -