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Titolo:
Analysis of the CD40/CD40L role in the sustenance of alloreactive antibodyproduction
Autore:
Shoker, AS; Lun, ZR; Choudry, R; Saxena, A;
Indirizzi:
Univ Saskatchewan, Dept Med, Saskatoon, SK S7N 0W8, Canada Univ Saskatchewan Saskatoon SK Canada S7N 0W8 skatoon, SK S7N 0W8, Canada Univ Saskatchewan, Dept Pathol, Saskatoon, SK S7N 0W8, Canada Univ Saskatchewan Saskatoon SK Canada S7N 0W8 skatoon, SK S7N 0W8, Canada
Titolo Testata:
TRANSPLANT IMMUNOLOGY
fascicolo: 4, volume: 8, anno: 2001,
pagine: 219 - 228
SICI:
0966-3274(200102)8:4<219:AOTCRI>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
MAJOR HISTOCOMPATIBILITY COMPLEX; RENAL-ALLOGRAFT REJECTION; POLYMERASE CHAIN-REACTION; CD40 LIGAND; B-CELLS; IN-VIVO; TRANSPLANT RECIPIENTS; CYTOKINE SYNTHESIS; HUMORAL IMMUNITY; QUANTITATIVE PCR;
Keywords:
alloreactive antibodies; CD40 ligand; SCID mice; gene expression;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
54
Recensione:
Indirizzi per estratti:
Indirizzo: Shoker, AS Royal Univ Hosp, Dept Med, Div Nephrol, 103 Hosp Dr, Saskatoon,SK S7N 0W8, Canada Royal Univ Hosp 103 Hosp Dr Saskatoon SK Canada S7N 0W8 Canada
Citazione:
A.S. Shoker et al., "Analysis of the CD40/CD40L role in the sustenance of alloreactive antibodyproduction", TRANSPL IMM, 8(4), 2001, pp. 219-228

Abstract

CD40 ligand (CD40L) is important for T/B lymphocyte interaction. To understand the cellular basis of humoral allosensitization we, therefore: (1) measured CD40L protein and gene expression in sensitized and non-sensitized uremic unactivated peripheral CD4(+) T lymphocytes; (2) studied the impact ofblocking the CD40/CD40L pathway on alloreactive antibody (allo-Ab) production by engrafted sensitized PBLs into severe combined immunodeficient (SCID) mice after in vitro preactivation with IL2/LPs/HLA class II allopeptides and adjuvants as a potent stimulus to produce allo-Ab (Shoker et al. Transplantation 1999;68;1188); and (3) studied the modifying effect of CD40/CD40Lblockade on T helper type I and II cytokine gene expression in the respective mice spleen. The CD40L protein was measured by dow cytometry and the gene expression was measured by quantitative RT-PCR. Alloreactive antibodies (alo-Abs) produced by sensitized PBLs engrafted into SCID mice with and without blockade of the CD40 receptor were measured by the PRA-STAT ELISA method. The modifying effects of CD40 blocking on allo-Ab production and cytokine gene expression by the engrafted cells measured by RT-PCR were then compared. There was no detectable CD40L protein expression in either the uremicor the control groups. The CD40L gene expression of 0.04 +/- 0.02 attomoles (aM) in the sensitized group was significantly higher than in the non-sensitized patients (0.009 +/- 0.007 aM, P < 0.0001) or the control CD-4(+) T cells (0.016 <plus/minus> 0.004 aM, P < 0.001). Blockade of the CD40 receptor abrogated the production of allo-Ab antibodies by the engrafted sensitized cells in 60% of the tested mice (n = 10); decreased the mean <plus/minus>S.D. optic density of allo-Ab to 0.1 +/- 0.13 and the mean +/- S.D. PRA to12 +/- 16). In the presence of the control Ab, allo-Ab production in SCID sera was present in 100% of the 10 SCID mice tested; the mean +/- S.D. PRA was 75 +/- 20, and the mean +/- S.D. OD activity was 0.412 +/- 0.17. All cytokine genes were, otherwise, expressed in the presence or absence of CD40 blockade. The results suggest a potential role of an enhanced CD40/CD40L interaction in the sustenance of alloreactive antibody production without significant deviation to T helper-like I or II responses. Blocking the CD40/CD40L pathway may have a potential therapeutic benefit to treat sensitized uremic patients. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/09/20 alle ore 20:40:27