Alcoholic liver cirrhosis is associated with a decreased expression of the CD28 costimulatory molecule, a lower ability of T cells to bind exogenous IL-2, and increased soluble CD8 levels.
Despite the existence of high interleukin (IL)-12 serum levels in patients with chronic active alcoholism, previous studies from our group have shown that, during active ethanol intake, alcoholic patients with alcoholic liver cirrhosis (ALC) display an impaired T-helper-1 response together with abnormalities in the peripheral blood (PB) cytotoxic compartment. The aim of the present study was to gain further insights into the mechanisms underlying these abnormalities. For that purpose, we analyzed the expression on PB B- and T-cell subsets of both the CD28 and CD80 costimulatory molecules, the ability of T lymphocytes to bind to exogenous recombinant IL-2, and the serum levels of soluble CD8 (sCD8) that might interfere with CD8+ T-cell activation in a group of 10 ALC patients with active ethanol intake (ALCET group). As reference groups, we analyzed 10 healthy individuals, 10 chronic alcoholic patients without liver disease (AWLD group) but with active ethanol intake, and 10 ALC patients who had quit drinking for at least 1 year. Our results showed that ALCET patients display a significant decrease in the number of PB CD28+/CD8(hi) T cells (P < 0.05) and CD80+ B cells (P < 0.01) compared with both healthy controls and AWLD patients. In addition, in ALCET patients, PB T cells also showed a decreased ability to bind to exogenous IL-2 (P < 0.01). This was associated with the existence of increased serum levels of sCD8 in ALC patients, the highest levels being detected in the ALCET group (P < 0.01). Altogether, our results point to the existence of several abnormalities that would affect the cytotoxic response in ALCET patients.
Laso
F J
FJ
Servicio de Medicina Interna II, Hospital Universitario de Salamanca, Salamanca, Spain. laso@gugu.usal.es
Iglesias-Osma
C
C
Ciudad
J
J
López
A
A
Pastor
I
I
Torres
E
E
Orfao
A
A
D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis / Q000097:blood; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000097:blood; D018106:CD28 Antigens / Q000096:biosynthesis* / Q000097:blood; D016827:CD8 Antigens / Q000096:biosynthesis / Q000097:blood*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D037181:Lectins, C-Type; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D011485:Protein Binding / Q000276:immunology; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D016827:CD8 Antigens; D007376:Interleukin-2; D037181:Lectins, C-Type; D000099192:CD69 Antigens