Similar abnormalities of idiotype and immunoglobulin light chain expression and of cell-mediated cytotoxicity in HIV-infected humans and simian immunodeficiency virus (SIV)-infected rhesus macaques.

Abstract

The pathogenesis of AIDS in simian immunodeficiency virus (SIV)-infected rhesus macaques models the pathogenesis of human AIDS. We investigated whether certain immunological abnormalities associated with HIV infection and implicated in disease progression also occur in SIV infection. We observed striking parallels between the rhesus macaque humoral immune response to SIV and unusual features of the human humoral immune response to HIV infection. Anti-SIV envelope antibodies from SIV-infected macaques exhibited skewed kappa/lambda L chain usage relative to the ratio of kappa/lambda L chain usage detected on total plasma Ig. In addition, the same idiotope conserved on human anti-HIV gag, pol and env antibodies was detected with a similar distribution pattern on macaque anti-SIV env, gag and pol antibodies. Skewed Ig L chain representation and selection of a highly conserved possible dominant regulatory idiotope on antibodies against key neutralizing antigens raise the possibility that the progressive failure of the humoral immune response to SIV and HIV involves skewed oligoclonal humoral immunity. We also found that SIV-infected macaques, like HIV-infected humans, have elevated levels of CD8+ lymphocyte-mediated cytotoxicity. Cytotoxicity against human B cells was higher in CD8+ effector lymphocytes from SIV-infected macaques than in those from uninfected macaques (P < 0.05). Cell-mediated cytotoxicity against human NK cell targets was not elevated in effector lymphocytes from the SIV-infected macaques, suggesting that CTL activity was selectively elevated. Two out of seven SIV-infected macaques tested had CD8+ cytotoxic lymphocytes that selectively killed activated uninfected CD4+ macaque lymphocytes. Oligoclonal B cell responses and persistently elevated CD8+ lymphocyte-mediated cytotoxicity are consistent features of primate retroviral infections leading to AIDS. Understanding immune predispositions to these features triggered by HIV and SIV may advance new prophylactic and therapeutic strategies.