Defective integration of activating signals derived from the T
cell receptor (TCR) and costimulatory molecules in both CD4+
and CD8+ T Lymphocytes of Common Variable immunodeficiency
(CVID) Patients

J 1997

Defective integration of activating signals derived from the T cell receptor (TCR) and costimulatory molecules in both CD4+ and CD8+ T Lymphocytes of Common Variable immunodeficiency (CVID) Patients

THON, Vojtěch, HM. WOLF, M. SASGARY, J. LITZMAN, A. SAMSTAG et. al.

Basic information

Original name

Defective integration of activating signals derived from the T cell receptor (TCR) and costimulatory molecules in both CD4+ and CD8+ T Lymphocytes of Common Variable immunodeficiency (CVID) Patients

Name in Czech

Porušená integrace aktivačních signálů TCR a kostimulačních molekul T lymfocytů u běžné variabilní imunodeficience (CVID)

Authors

THON, Vojtěch (203 Czech Republic, guarantor), HM. WOLF (40 Austria), M. SASGARY (40 Austria), J. LITZMAN (203 Czech Republic), A. SAMSTAG (40 Austria), I. HAUBER (276 Germany), J. LOKAJ (203 Czech Republic) and MM. EIBL (40 Austria)

Edition

Clin.Exp.Immunol. 1997, 0009-9104

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30102 Immunology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 2.506

RIV identification code

RIV/00216224:14110/97:00030214

Organization unit

Faculty of Medicine

UT WoS

A1997YF65000005

Keywords (in Czech)

CVID; integrace signálů; CD40L

Keywords in English

common variable immunodeficiency; activation; costimulation; T cell receptor; CD40 ligand

Abstract

ORIG CZ

V originále

CVID is characterized by hypogammaglobulinaemia and impaired antibody production. Previous studies demonstrated defects at the T cell level. In the present study the response of purified CD4(+) and CD8(+) T lymphocytes to stimulation with anti-TCR monoclonal antibody (the first signal) in combination with anti-CD4 or anti-CD8, anti-CD2 and anti-CD28 MoAbs (the costimulatory signals) was investigated. Both CD4(+) and CD8(+)T cells from the patients showed significantly reduced IL-2 release following stimulation via TCR and costimulation via CD4 or CD8 and CD2, respectively. However, normal IL-2 production following TCR plus phorbol myristate acetate (PMA) costimulation and normal expression of an early activation marker, CD69, after TCR + CD28 stimulation indicated that TCR was able to transduce a signal. Furthermore, both IL-2 and IL-4 release were impaired in CD4(+) lymphocytes following TCR+CD28 stimulation. In addition,stimulation via TCR+CD28 resulted in significantly decreased expression of CD40 Ligand in the patients. These results suggest that the integration of activating signals derived from the TCR and costimulatory molecules is defective in CVID patients; the defect is not confined to costimulation via a single molecule, or restricted to cells producing Th1-type cytokines such as IL-2, and is expressed in both CD4(+) and CD8(+) T cell subsets.

In Czech

Porušená integrace aktivačních signálů TCR a kostimulačních molekul T lymfocytů u běžné variabilní imunodeficience (CVID).

Citovat

THON, Vojtěch, HM. WOLF, M. SASGARY, J. LITZMAN, A. SAMSTAG, I. HAUBER, J. LOKAJ and MM. EIBL. Defective integration of activating signals derived from the T cell receptor (TCR) and costimulatory molecules in both CD4+ and CD8+ T Lymphocytes of Common Variable immunodeficiency (CVID) Patients. Clin.Exp.Immunol. 1997, vol. 31, No 3, p. 174-181. ISSN 0009-9104.

@article{192404,
   author = {Thon, Vojtěch and Wolf, HM. and Sasgary, M. and Litzman, J. and Samstag, A. and Hauber, I. and Lokaj, J. and Eibl, MM.},
   article_number = {3},
   keywords = {common variable immunodeficiency; activation; costimulation; T cell receptor; CD40 ligand},
   language = {eng},
   issn = {0009-9104},
   journal = {Clin.Exp.Immunol.},
   title = {Defective integration of activating signals derived from the T cell receptor (TCR) and costimulatory molecules in both CD4+ and CD8+ T Lymphocytes of Common Variable immunodeficiency (CVID) Patients},
   volume = {31},
   year = {1997}
}

TY  - JOUR
ID  - 192404
AU  - Thon, Vojtěch - Wolf, HM. - Sasgary, M. - Litzman, J. - Samstag, A. - Hauber, I. - Lokaj, J. - Eibl, MM.
PY  - 1997
TI  - Defective integration of activating signals derived from the T cell receptor (TCR) and costimulatory molecules in both CD4+ and CD8+ T Lymphocytes of Common Variable immunodeficiency (CVID) Patients
JF  - Clin.Exp.Immunol.
VL  - 31
IS  - 3
SP  - 174
EP  - 174
SN  - 00099104
KW  - common variable immunodeficiency
KW  - activation
KW  - costimulation
KW  - T cell receptor
KW  - CD40 ligand
N2  - CVID is characterized by hypogammaglobulinaemia and impaired antibody production. Previous studies demonstrated defects at the T cell level. In the present study the response of purified CD4(+) and CD8(+) T lymphocytes to stimulation with anti-TCR monoclonal antibody (the first signal) in combination with anti-CD4 or anti-CD8, anti-CD2 and anti-CD28 MoAbs (the costimulatory signals) was investigated. Both CD4(+) and CD8(+)T cells from the patients showed significantly reduced IL-2 release following stimulation via TCR and costimulation via CD4 or CD8 and CD2, respectively. However, normal IL-2 production following TCR plus phorbol myristate acetate (PMA) costimulation and normal expression of an early activation marker, CD69, after TCR + CD28 stimulation indicated that TCR was able to transduce a signal. Furthermore, both IL-2 and IL-4 release were impaired in CD4(+) lymphocytes following TCR+CD28 stimulation. In addition,stimulation via TCR+CD28 resulted in significantly decreased expression of CD40 Ligand in the patients. These results suggest that the integration of activating signals derived from the TCR and costimulatory molecules is defective in CVID patients; the defect is not confined to costimulation via a single molecule, or restricted to cells producing Th1-type cytokines such as IL-2, and is expressed in both CD4(+) and CD8(+) T cell subsets.
ER  -

THON, Vojtěch, HM. WOLF, M. SASGARY, J. LITZMAN, A. SAMSTAG, I. HAUBER, J. LOKAJ and MM. EIBL. Defective integration of activating signals derived from the T cell receptor (TCR) and costimulatory molecules in both CD4+ and CD8+ T Lymphocytes of Common Variable immunodeficiency (CVID) Patients. \textit{Clin.Exp.Immunol.}. 1997, vol.~31, No~3, p.~174-181. ISSN~0009-9104.

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