Pathogenic disorders involved in immunosuppression and T cell depletion characterizing AIDS.
Four cardinal immune disorders interacting with each other may promote the progressive T cell depletion and immunosuppression characterizing AIDS. Immune activation of HIV-1 infected T4 cells leads to virus release and premature cell death. Both virus release with its resulting viral load and dead cells are the source of gp120 stimulus. Anergy of non-infected CD4 cells, resulting in cytokine dysregulation may be promoted by impairing the CD4-MHC interaction during CD4 cell activation either directly through the SLWDQ pentapeptide identity with the CD4 molecule and the CD4 binding region or through a gp120-induced autoimmune reaction to CD4. Overproduction of IFN alpha, the known antiproliferative and cytolytic cytokine may promote in a paracrine manner to neighbouring cells the immunosuppression generated by the lack of IL2 secretion following CD4 cell anergy. Apoptosis of activated non infected T cells could be induced by effector components of the autoimmune reaction (CTL, Lymphotoxins or Abs?) directed towards the 2 consensus gp120 sequence identity/similarity (INCTR and FYCNST) shared with the APO/Fas molecule. These two sequences are known as immunodominant sites of the gp120. Furthermore, IFN alpha overproduction may also render circulating memory T cells competent to apoptosis by upregulating the cascade of metabolic events leading to programmed cell death.
Zagury
J F
JF
Université P and M Curie, Laboratorie de Physiologie Cellulaire, Paris, France.
Lachgar
A
A
Achour
A
A
Chams-Harvey
V
V
Cho
Y Y
YY
Le Coq
H
H
Bizzini
B
B
Feldman
M
M
Burny
A
A
Zagury
D
D
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015497:HIV-1; D006801:Humans; D007108:Immune Tolerance; D016898:Interferon-alpha / Q000096:biosynthesis; D008212:Lymphocyte Depletion; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D015699:HIV Envelope Protein gp120; D016898:Interferon-alpha