Enhanced T-cell apoptosis in human septic shock is associated with alteration of the costimulatory pathway.
T-cell apoptosis during septic shock (SS) has been associated with deleterious outcome, but the mechanisms of apoptosis are not well understood. As T-cells are not infected in bacterial infection, our hypothesis was that deleterious interactions between lymphocytes and monocytes could be involved. This is a cross-sectional study of 27 patients presenting with community-acquired SS, 23 infected patients without SS and 18 controls. Cytofluorometric techniques were used to study apoptosis, the costimulatory pathway and cytokine synthesis. Apoptosis was increased in SS compared to infected patients without SS and controls: the median values were 18, 2 and 3%, respectively, for CD4(+) T-cells (P < 0.001), and 12, 5 and 2%, respectively, for CD8(+) T-cells (P < 0.001). Patients with SS exhibited significant CD152 over-expression on T-cells, while CD86 expression was decreased on monocytes (P = 0.004). The synthesis of interleukin-2 was decreased in patients with SS compared to the other groups, while secretions of interferon-gamma and TNF-alpha were not altered. Ten surviving patients with SS showed a trend towards the normalisation of these parameters on day 7. In SS, T-cell apoptosis is related, at least in part, to the alteration of the costimulatory pathway, which, in turn, leads to significant modification of the cytokine network.
Roger
P-M
PM
Service d'Infectiologie, Centre Hospitalier Universitaire de Nice, Nice, France. roger.pm@chu-nice.fr
Hyvernat
H
H
Breittmayer
J-P
JP
Dunais
B
B
Dellamonica
J
J
Bernardin
G
G
Bernard
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000096:biosynthesis; D017209:Apoptosis; D051940:B7-2 Antigen / Q000096:biosynthesis; D060908:CTLA-4 Antigen; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D012772:Shock, Septic / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015703:Antigens, CD; D051940:B7-2 Antigen; C497964:CD86 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma