Autoimmune T-cell response to the CD4 molecule in HIV-infected patients.
In a previous study, we demonstrated that by downregulating plasma membrane CD4 and increasing its processing, human immunodeficiency (HIV)-1-gp120 unveils hidden CD4 epitopes, inducing an in vitro anti-CD4-specific T-cell response. We report herein that this mechanism may potentially have important implications in HIV immunopathogenesis, because it could take part in the severe depletion of CD4+ cells that characterizes acquired immune deficiency syndrome (AIDS) and be related to disease progression. Freshly isolated peripheral blood lymphocytes (PBMC) from about 1/4 of a conspicuous cohort of HIV-infected patients responded to CD4 and this response was correlated with beta2-microglobulin levels, widely recognized as marker for progression of HIV infection. Moreover, we provide evidence that a CD4-specific T cell priming can occur in vivo, following a gp120 or anti-CD4 monoclonal antibody (mAb)-mediated CD4 molecule downregulation on antigen-presenting cells (APC). To our knowledge, this is the first study indicating that an autoimmune T-cell response is linked to HIV infection and that it could have an important impact on the immunopathogenesis of this disease.
Caporossi
A P
AP
Istituto I Clinica Medica, Università di Roma La Sapienza, Rome, Italy.
Bruno
G
G
Salemi
S
S
Mastroianni
C
C
Falciano
M
M
Salotti
A
A
Bergami
N
N
Santilio
I
I
Nisini
R
R
Barnaba
V
V
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015536:Down-Regulation; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013745:Tetanus Toxoid / Q000276:immunology; D014373:Tuberculin / Q000276:immunology
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D000949:Histocompatibility Antigens Class II; D013745:Tetanus Toxoid; D014373:Tuberculin