Monosomy 1p36 uncovers a role for OX40 in survival of activated CD4+ T cells

M. M. Suhoski, E. E. Perez, M. L. Heltzer, A. Laney, L. G. Shaffer, S. Saitta, S. Nachman, N. B. Spinner, C. H. June, J. S. Orange

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Monosomy 1p36 is a subtelomeric deletion syndrome associated with congenital anomalies presumably due to haploinsufficiency of multiple genes. Although immunodeficiency has not been reported, genes encoding costimulatory molecules of the TNF receptor superfamily (TNFRSF) are within 1p36 and may be affected. In one patient with monosomy 1p36, comparative genome hybridization and fluorescence in- situ hybridization confirmed that TNFRSF member OX40 was included within the subtelomeric deletion. T cells from this patient had decreased OX40 expression after stimulation. Specific, ex vivo T cell activation through OX40 revealed enhanced proliferation, and reduced viability of patient CD4+ T cells, providing evidence for the association of monosomy 1p36 with reduced OX40 expression, and decreased OX40-induced T cell survival. These results support a role for OX40 in human immunity, and calls attention to the potential for haploinsufficiency deletions of TNFRSF costimulatory molecules in monosomy 1p36.

Original languageEnglish
Pages (from-to)181-189
Number of pages9
JournalClinical Immunology
Volume128
Issue number2
DOIs
StatePublished - Aug 1 2008

Fingerprint

Monosomy
Tumor Necrosis Factor Receptors
T-Lymphocytes
Haploinsufficiency
Survival
Comparative Genomic Hybridization
Fluorescence In Situ Hybridization
Genes
In Situ Hybridization
Immunity
Cell Survival

Keywords

  • 1p36
  • 4-1BB
  • OX40
  • Primary immunodeficiency
  • Subtelomeric deletion
  • T cell memory
  • TNFRSF superfamily

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Suhoski, M. M., Perez, E. E., Heltzer, M. L., Laney, A., Shaffer, L. G., Saitta, S., ... Orange, J. S. (2008). Monosomy 1p36 uncovers a role for OX40 in survival of activated CD4+ T cells. Clinical Immunology, 128(2), 181-189. https://doi.org/10.1016/j.clim.2008.03.522

Monosomy 1p36 uncovers a role for OX40 in survival of activated CD4+ T cells. / Suhoski, M. M.; Perez, E. E.; Heltzer, M. L.; Laney, A.; Shaffer, L. G.; Saitta, S.; Nachman, S.; Spinner, N. B.; June, C. H.; Orange, J. S.

In: Clinical Immunology, Vol. 128, No. 2, 01.08.2008, p. 181-189.

Research output: Contribution to journalArticle

Suhoski, MM, Perez, EE, Heltzer, ML, Laney, A, Shaffer, LG, Saitta, S, Nachman, S, Spinner, NB, June, CH & Orange, JS 2008, 'Monosomy 1p36 uncovers a role for OX40 in survival of activated CD4+ T cells', Clinical Immunology, vol. 128, no. 2, pp. 181-189. https://doi.org/10.1016/j.clim.2008.03.522
Suhoski MM, Perez EE, Heltzer ML, Laney A, Shaffer LG, Saitta S et al. Monosomy 1p36 uncovers a role for OX40 in survival of activated CD4+ T cells. Clinical Immunology. 2008 Aug 1;128(2):181-189. https://doi.org/10.1016/j.clim.2008.03.522
Suhoski, M. M. ; Perez, E. E. ; Heltzer, M. L. ; Laney, A. ; Shaffer, L. G. ; Saitta, S. ; Nachman, S. ; Spinner, N. B. ; June, C. H. ; Orange, J. S. / Monosomy 1p36 uncovers a role for OX40 in survival of activated CD4+ T cells. In: Clinical Immunology. 2008 ; Vol. 128, No. 2. pp. 181-189.
@article{7f02dab27ece4835a52c7b4cc57455e8,
title = "Monosomy 1p36 uncovers a role for OX40 in survival of activated CD4+ T cells",
abstract = "Monosomy 1p36 is a subtelomeric deletion syndrome associated with congenital anomalies presumably due to haploinsufficiency of multiple genes. Although immunodeficiency has not been reported, genes encoding costimulatory molecules of the TNF receptor superfamily (TNFRSF) are within 1p36 and may be affected. In one patient with monosomy 1p36, comparative genome hybridization and fluorescence in- situ hybridization confirmed that TNFRSF member OX40 was included within the subtelomeric deletion. T cells from this patient had decreased OX40 expression after stimulation. Specific, ex vivo T cell activation through OX40 revealed enhanced proliferation, and reduced viability of patient CD4+ T cells, providing evidence for the association of monosomy 1p36 with reduced OX40 expression, and decreased OX40-induced T cell survival. These results support a role for OX40 in human immunity, and calls attention to the potential for haploinsufficiency deletions of TNFRSF costimulatory molecules in monosomy 1p36.",
keywords = "1p36, 4-1BB, OX40, Primary immunodeficiency, Subtelomeric deletion, T cell memory, TNFRSF superfamily",
author = "Suhoski, {M. M.} and Perez, {E. E.} and Heltzer, {M. L.} and A. Laney and Shaffer, {L. G.} and S. Saitta and S. Nachman and Spinner, {N. B.} and June, {C. H.} and Orange, {J. S.}",
year = "2008",
month = "8",
day = "1",
doi = "10.1016/j.clim.2008.03.522",
language = "English",
volume = "128",
pages = "181--189",
journal = "Clinical Immunology",
issn = "1521-6616",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Monosomy 1p36 uncovers a role for OX40 in survival of activated CD4+ T cells

AU - Suhoski, M. M.

AU - Perez, E. E.

AU - Heltzer, M. L.

AU - Laney, A.

AU - Shaffer, L. G.

AU - Saitta, S.

AU - Nachman, S.

AU - Spinner, N. B.

AU - June, C. H.

AU - Orange, J. S.

PY - 2008/8/1

Y1 - 2008/8/1

N2 - Monosomy 1p36 is a subtelomeric deletion syndrome associated with congenital anomalies presumably due to haploinsufficiency of multiple genes. Although immunodeficiency has not been reported, genes encoding costimulatory molecules of the TNF receptor superfamily (TNFRSF) are within 1p36 and may be affected. In one patient with monosomy 1p36, comparative genome hybridization and fluorescence in- situ hybridization confirmed that TNFRSF member OX40 was included within the subtelomeric deletion. T cells from this patient had decreased OX40 expression after stimulation. Specific, ex vivo T cell activation through OX40 revealed enhanced proliferation, and reduced viability of patient CD4+ T cells, providing evidence for the association of monosomy 1p36 with reduced OX40 expression, and decreased OX40-induced T cell survival. These results support a role for OX40 in human immunity, and calls attention to the potential for haploinsufficiency deletions of TNFRSF costimulatory molecules in monosomy 1p36.

AB - Monosomy 1p36 is a subtelomeric deletion syndrome associated with congenital anomalies presumably due to haploinsufficiency of multiple genes. Although immunodeficiency has not been reported, genes encoding costimulatory molecules of the TNF receptor superfamily (TNFRSF) are within 1p36 and may be affected. In one patient with monosomy 1p36, comparative genome hybridization and fluorescence in- situ hybridization confirmed that TNFRSF member OX40 was included within the subtelomeric deletion. T cells from this patient had decreased OX40 expression after stimulation. Specific, ex vivo T cell activation through OX40 revealed enhanced proliferation, and reduced viability of patient CD4+ T cells, providing evidence for the association of monosomy 1p36 with reduced OX40 expression, and decreased OX40-induced T cell survival. These results support a role for OX40 in human immunity, and calls attention to the potential for haploinsufficiency deletions of TNFRSF costimulatory molecules in monosomy 1p36.

KW - 1p36

KW - 4-1BB

KW - OX40

KW - Primary immunodeficiency

KW - Subtelomeric deletion

KW - T cell memory

KW - TNFRSF superfamily

UR - http://www.scopus.com/inward/record.url?scp=46749085819&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=46749085819&partnerID=8YFLogxK

U2 - 10.1016/j.clim.2008.03.522

DO - 10.1016/j.clim.2008.03.522

M3 - Article

C2 - 18511345

AN - SCOPUS:46749085819

VL - 128

SP - 181

EP - 189

JO - Clinical Immunology

JF - Clinical Immunology

SN - 1521-6616

IS - 2

ER -