CD40L, CD28, and CTLA-4 expression on CD4+ T cells in kidney graft recipients: a relationship with post-transplantation clinical course.
BACKGROUND
Experimental studies have demonstrated that the intensity of alloreactivity against a transplanted organ results from an interaction of positive (CD40/CD40L and B.7/CD28) and inhibitory (B.7/CTLA-4) signals between antigen-presenting cells (APCs) and T lymphocytes.


METHODS
We examined the CD40L, CD28, and both surface (s) and intracellular (i) CTLA-4 expressions on freshly drawn and anti-CD3+rIL-2-stimulated peripheral blood CD4+ T cells in groups of kidney transplant recipients in relation to distinct clinical course using the tri-color immunofluorescence method.


RESULTS
The median proportions of freshly isolated CD3+/CD4+/CTLA-4+ and CD3+/CD4+/CD40L+ cells in all groups of graft recipients were higher than in control subjects. In patients with stable graft function (SGF), non-significantly higher sCTLA-4, significantly higher iCTLA-4 expression, and significantly lower CD40L expression on freshly drawn CD4+ T cells compared with recipients with chronic allograft nephropathy (CAN) were found. Moreover, CD4+ T cells from SGF patients showed a higher potential to express sCTLA-4 and CD40L molecules and to down-regulate the CD28 molecule in response to ex vivo stimulation than those from patients with CAN. In patients without acute graft rejection (NAGR), a markedly higher proportion of freshly drawn CD3+/CD4+/iCTLA-4+ cells compared with patients with acute graft rejection (AGR) and an up-regulation of the median percentage of CD3+/CD4+/CD40L+ cells after ex vivo stimulation was found.


CONCLUSIONS
In patients with SGF, peripheral blood CD4+ T cells exhibited a higher potential to express surface CTLA-4 and CD40L and to down-regulate CD28 costimulatory molecules in response to ex vivo stimulation, indicating a relationship between the expression patterns of both costimulatory and inhibitory molecules in CD4+ T cells and clinical course after renal transplantation.
Kosmaczewska
Agata
A
Department of Experimental Therapy, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland. kosmacz@immuno.iitd.pan.wroc.pl
Magott-Procelewska
Maria
M
Frydecka
Irena
I
Ciszak
Lidia
L
Bocko
Dorota
D
Szteblich
Aleksandra
A
Kusnierczyk
Piotr
P
Patrzalek
Dariusz
D
Szyber
Piotr
P
Klinger
Marian
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis* / Q000502:physiology; D000943:Antigens, Differentiation / Q000096:biosynthesis* / Q000502:physiology; D018106:CD28 Antigens / Q000096:biosynthesis* / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D023201:CD40 Ligand / Q000096:biosynthesis* / Q000502:physiology; D060908:CTLA-4 Antigen; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016030:Kidney Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000502:physiology; D008875:Middle Aged; D011184:Postoperative Period
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D008565:Membrane Proteins; D023201:CD40 Ligand