Detection of simian immunodeficiency virus (SIV)‐specific T‐cell‐mediated cytotoxicity in the peripheral blood from infected cynomolgus monkeys

Abstract

We have previously demonstrated that peptide immunization restimulates the memory CD4 T-cell response, but fails to induce cytotoxic T lymphocyte (CTL) in cynomolgus macaques. To examine the nature of protective immunity to simian immunodeficiency virus (SIV) in this study, freshly isolated peripheral blood mononuclear cells (PBMC) from four infected juvenile cynomolgus macaques and from three uninfected control macaques were assessed for CTL activity monthly for 9 consecutive months, beginning 1 month after detection of infection. Target cells consisted of major histocompatibility (MHC) haploidentical parental PBMC which were stimulated with mitogen and then pulsed with heat-killed SIVcyn. CTL activity was demonstrated in PBMCs from all four infected animals. The effector cells are T cells which mediate cytotoxicity against SIVcyn-pulsed target cells in an MHC-restricted manner. Furthermore, the cytotoxicity is virus specific and predominantly, if not exclusively, mediated by CD8+ T cells; it is also MHC class I restricted. Incubation of target cells with pepstatin A during antigen pulsing prior to the cytotoxic assay inhibited target cell generation, suggesting that viral antigens are processed via an endocytic pathway.

Comparative analysis of natural killer cell activity, lymphoproliferation and lymphocyte surface antigen expression in nonhuman primates housed at the CIRMF Primate Center, Gabon

“…The high NK cell lytic activity observed in the rhesus monkey PBMCs may be due in part to CD56 + NK cells and in part to cells expressing a phenotype different from CD56 or to cells belonging to the T-lymphocyte lineage [42]. Furthermore, we have previously shown that NK activity could be decreased by lysis of effector cells with anti-CD56 in SIV cyn -infected cynomolgus monkeys [29]. The NK cell activity shown by PBMCs was different for cynomolgus monkeys and rhesus monkeys compared with mandrills and vervets.…”

“…NK cells represent an important first line of defense against viral infections, against neoplastic cell growth, and in the control of hematopoiesis [1,13,46]. Previous studies have examined the NK cell activity in some primate species (e.g., rhesus monkeys [Macaca mulatta] and cynomolgus monkeys [Macaca fascicularis]), and the cells responsible for the observed cytotoxicity activity have been, in some instances, characterized [6,27,29,55]. It was reported that the onset of human AIDS correlates with an impairment of NK cell functions [7,45].…”