Role of CD95-activated caspase-1 processing of IL-1beta in TCR-mediated proliferation of HIV-infected CD4(+) T cells.
CD95 plays a critical role in the homeostasis of the immune system, and has been reported to participate in T cell death during HIV infection. Here we report that the response to CD3-TCR stimulation of CD4(+) T cells from HIV-infected individuals and CD4(+) T cells from healthy donors incubated in vitro with HIV-1(Lai) depends on the manner the CD3-TCR complex is engaged. While stimulation by anti-CD3 antibodies in solution induced CD4 T cell apoptosis both in the absence or presence of anti-CD95 antibodies, stimulation by immobilized anti-CD3 antibodies rendered CD4(+) T cells resistant to CD95-mediated death and led to increased CD4 T cell proliferation in response to CD95 ligation. CD95 ligation of CD4(+) T cells led to the activation of caspases, while costimulation induced by anti-CD3 and anti-CD95 mAb prevented the full processing of caspase-3 and caspase-8. Proliferation of CD4(+) T cells induced by CD3-TCR and CD95 costimulation was decreased by treatments with a caspase-1 inhibitor or with neutralizing antibodies to IL-1ss, indicating a requirement for caspase-1-mediated IL-1beta processing and secretion. Our findings suggest a novel mechanism whereby in addition to its role in inducing T cell apoptosis, CD95 signaling during HIV infection may also provide a costimulatory signal leading to an enhancement of CD4 T cell proliferation in response to CD3-TCR complex engagement.
Petit
F
F
EMI-U 9922, INSERM/Université Paris 7, CHU Bichat-Claude Bernard, Paris, France.
Corbeil
J
J
Lelièvre
J D
JD
Moutouh-de Parseval
L
L
Pinon
G
G
Green
D R
DR
Ameisen
J C
JC
Estaquier
J
J
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D020170:Caspase 1 / Q000502:physiology*; D002478:Cells, Cultured; D004789:Enzyme Activation; D015497:HIV-1; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D008213:Lymphocyte Activation; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000502:physiology*; D019014:fas Receptor / Q000502:physiology*
D007375:Interleukin-1; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D019014:fas Receptor; D020170:Caspase 1