Down-regulation of IL-2 receptor α (CD25) characterizes human γδ-T cells rendered resistant to apoptosis after CD2 engagement in the presence of IL-12

B. L. Guo, K. A. Hollmig, R. D. Lopez

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

We recently identified a CD2-mediated, IL-12-dependent signaling pathway that inhibits apoptosis in mitogen-stimulated human γδ-T cells. Here we show that γδ-T cells which acquire resistance to mitogen-induced apoptosis upregulate IL-12 receptor beta 1 subunit (IL-12Rβ1); in contrast, γδ-T cells which remain sensitive to mitogen-induced apoptosis fail to express IL-12Rβ1. Next we show that γδ-T cells which are rendered resistant to mitogen-induced apoptosis attenuate their expression of the IL-2 receptor α chain (IL-2Rα/CD25), this in part accounting for their acquired resistance to IL-2-induced death. In contrast, apoptosissensitive γδ-T cells are shown to persist in their expression of IL-2Rα/CD25, thus remaining sensitive to IL-2-induced death. Moreover, we show that apoptosisresistant, but not apoptosis-sensitive, γδ-T cells display an enhanced responsiveness to IL-15, a finding in keeping with the known function of IL-15 as a growth and survival factor. Finally, we present evidence to suggest that this differential responsiveness to IL-15 occurs in part by the increased expression of the IL-15Rα chain on apoptosis-resistant γδ-T cells, compared to apoptosis-sensitive γδ-T cells. The biological and clinical implications of these findings are discussed.

Original languageEnglish (US)
Pages (from-to)625-637
Number of pages13
JournalCancer Immunology, Immunotherapy
Volume50
Issue number11
DOIs
StatePublished - 2001

Fingerprint

Interleukin-2 Receptors
Interleukin-12
Down-Regulation
Apoptosis
T-Lymphocytes
Mitogens
Interleukin-15
Interleukin-12 Receptors
Interleukin-2
Intercellular Signaling Peptides and Proteins
Up-Regulation
Survival

Keywords

  • γδ-T cells
  • IL-15
  • IL-2 receptor
  • Immunotherapy

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Oncology

Cite this

Down-regulation of IL-2 receptor α (CD25) characterizes human γδ-T cells rendered resistant to apoptosis after CD2 engagement in the presence of IL-12. / Guo, B. L.; Hollmig, K. A.; Lopez, R. D.

In: Cancer Immunology, Immunotherapy, Vol. 50, No. 11, 2001, p. 625-637.

Research output: Contribution to journalArticle

@article{687edd141a104518884149b6f7ad47a3,
title = "Down-regulation of IL-2 receptor α (CD25) characterizes human γδ-T cells rendered resistant to apoptosis after CD2 engagement in the presence of IL-12",
abstract = "We recently identified a CD2-mediated, IL-12-dependent signaling pathway that inhibits apoptosis in mitogen-stimulated human γδ-T cells. Here we show that γδ-T cells which acquire resistance to mitogen-induced apoptosis upregulate IL-12 receptor beta 1 subunit (IL-12Rβ1); in contrast, γδ-T cells which remain sensitive to mitogen-induced apoptosis fail to express IL-12Rβ1. Next we show that γδ-T cells which are rendered resistant to mitogen-induced apoptosis attenuate their expression of the IL-2 receptor α chain (IL-2Rα/CD25), this in part accounting for their acquired resistance to IL-2-induced death. In contrast, apoptosissensitive γδ-T cells are shown to persist in their expression of IL-2Rα/CD25, thus remaining sensitive to IL-2-induced death. Moreover, we show that apoptosisresistant, but not apoptosis-sensitive, γδ-T cells display an enhanced responsiveness to IL-15, a finding in keeping with the known function of IL-15 as a growth and survival factor. Finally, we present evidence to suggest that this differential responsiveness to IL-15 occurs in part by the increased expression of the IL-15Rα chain on apoptosis-resistant γδ-T cells, compared to apoptosis-sensitive γδ-T cells. The biological and clinical implications of these findings are discussed.",
keywords = "γδ-T cells, IL-15, IL-2 receptor, Immunotherapy",
author = "Guo, {B. L.} and Hollmig, {K. A.} and Lopez, {R. D.}",
year = "2001",
doi = "10.1007/s00262-001-0244-4",
language = "English (US)",
volume = "50",
pages = "625--637",
journal = "Cancer Immunology and Immunotherapy",
issn = "0340-7004",
publisher = "Springer Science and Business Media Deutschland GmbH",
number = "11",

}

TY - JOUR

T1 - Down-regulation of IL-2 receptor α (CD25) characterizes human γδ-T cells rendered resistant to apoptosis after CD2 engagement in the presence of IL-12

AU - Guo, B. L.

AU - Hollmig, K. A.

AU - Lopez, R. D.

PY - 2001

Y1 - 2001

N2 - We recently identified a CD2-mediated, IL-12-dependent signaling pathway that inhibits apoptosis in mitogen-stimulated human γδ-T cells. Here we show that γδ-T cells which acquire resistance to mitogen-induced apoptosis upregulate IL-12 receptor beta 1 subunit (IL-12Rβ1); in contrast, γδ-T cells which remain sensitive to mitogen-induced apoptosis fail to express IL-12Rβ1. Next we show that γδ-T cells which are rendered resistant to mitogen-induced apoptosis attenuate their expression of the IL-2 receptor α chain (IL-2Rα/CD25), this in part accounting for their acquired resistance to IL-2-induced death. In contrast, apoptosissensitive γδ-T cells are shown to persist in their expression of IL-2Rα/CD25, thus remaining sensitive to IL-2-induced death. Moreover, we show that apoptosisresistant, but not apoptosis-sensitive, γδ-T cells display an enhanced responsiveness to IL-15, a finding in keeping with the known function of IL-15 as a growth and survival factor. Finally, we present evidence to suggest that this differential responsiveness to IL-15 occurs in part by the increased expression of the IL-15Rα chain on apoptosis-resistant γδ-T cells, compared to apoptosis-sensitive γδ-T cells. The biological and clinical implications of these findings are discussed.

AB - We recently identified a CD2-mediated, IL-12-dependent signaling pathway that inhibits apoptosis in mitogen-stimulated human γδ-T cells. Here we show that γδ-T cells which acquire resistance to mitogen-induced apoptosis upregulate IL-12 receptor beta 1 subunit (IL-12Rβ1); in contrast, γδ-T cells which remain sensitive to mitogen-induced apoptosis fail to express IL-12Rβ1. Next we show that γδ-T cells which are rendered resistant to mitogen-induced apoptosis attenuate their expression of the IL-2 receptor α chain (IL-2Rα/CD25), this in part accounting for their acquired resistance to IL-2-induced death. In contrast, apoptosissensitive γδ-T cells are shown to persist in their expression of IL-2Rα/CD25, thus remaining sensitive to IL-2-induced death. Moreover, we show that apoptosisresistant, but not apoptosis-sensitive, γδ-T cells display an enhanced responsiveness to IL-15, a finding in keeping with the known function of IL-15 as a growth and survival factor. Finally, we present evidence to suggest that this differential responsiveness to IL-15 occurs in part by the increased expression of the IL-15Rα chain on apoptosis-resistant γδ-T cells, compared to apoptosis-sensitive γδ-T cells. The biological and clinical implications of these findings are discussed.

KW - γδ-T cells

KW - IL-15

KW - IL-2 receptor

KW - Immunotherapy

UR - http://www.scopus.com/inward/record.url?scp=0035678634&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035678634&partnerID=8YFLogxK

U2 - 10.1007/s00262-001-0244-4

DO - 10.1007/s00262-001-0244-4

M3 - Article

C2 - 11807626

AN - SCOPUS:0035678634

VL - 50

SP - 625

EP - 637

JO - Cancer Immunology and Immunotherapy

JF - Cancer Immunology and Immunotherapy

SN - 0340-7004

IS - 11

ER -