Factors that influence activated CD8+ T-cell apoptosis in patients with acute herpesvirus infections: loss of costimulatory molecules CD28, CD5 and CD6 but relative maintenance of Bax and Bcl-X expression.
The expanded CD8+ T-lymphocyte population arising in response to viral infection controls the virus but could also prove damaging to the host unless safely removed at the end of the immune response. Apoptosis provides a mechanism whereby this can be achieved, as apoptotic cells are recognized and engulfed by macrophages. Peripheral blood CD8+ T lymphocytes from individuals with acute viral infections were highly susceptible to apoptosis after short-term culture in vitro. This spontaneous cell death could be prevented by interleukin-2 (IL-2) and was related to a decreased expression of Bcl-2 but not Bax or Bcl-XL, additional molecules that promote or prevent apoptosis, respectively, as well as an increase in CD95. After stimulation with anti-CD3 antibody, T cells from these patients also underwent an activation-induced cell death (AICD) that could not be prevented by IL-2. Interestingly, CD8+ T cells from this patient group expressed lower than normal levels of three costimulatory molecules, CD28, CD5 and CD6, suggesting that stimulation in the absence of a second signal is a possible mechanism for the defective reactivation of these cells. Thus multiple mechanisms, including loss of Bcl-2, increased CD95 and loss of costimulatory molecules, place constraints on the survival and reactivation of activated CD8+ T cells after viral infections. This enables immune activation to be controlled and cellular homeostasis to be re-established during resolution of viral diseases in vivo.
Borthwick
N J
NJ
Department of Clinical Immunology, Royal Free Hospital and School of Medicine, London, UK.
Bofill
M
M
Hassan
I
I
Panayiotidis
P
P
Janossy
G
G
Salmon
M
M
Akbar
A N
AN
D000208:Acute Disease; D015703:Antigens, CD / Q000097:blood; D000945:Antigens, Differentiation, T-Lymphocyte / Q000097:blood; D017209:Apoptosis / Q000276:immunology*; D018106:CD28 Antigens / Q000097:blood; D018956:CD5 Antigens / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018929:Cell Culture Techniques; D002455:Cell Division / Q000276:immunology; D002644:Chickenpox / Q000276:immunology; D006566:Herpesviridae Infections / Q000276:immunology*; D004854:Herpesvirus 4, Human; D006801:Humans; D015151:Immunoblotting; D011518:Proto-Oncogene Proteins / Q000097:blood; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D018106:CD28 Antigens; D018956:CD5 Antigens; C062279:CD6 antigen; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein