Immune Response against Vaccinia Virus in Rhesus Monkeys: No Evidence for Primary MHC-Restricted Cytolytic T Cells

Abstract

Rhesus monkeys were tested in vitro for their cellular immune response after infection with vaccinia virus, employing lymphocyte preparations from various lymphoid tissues. Although virus-infected target cells were lysed by lymphoid cells from immunized, but not from uninfected, rhesus monkeys, we could neither find evidence for MHC-restricted T cells nor for antibody-dependent cellular cytotoxicity. Kinetics of target cell lysis, the killing patterns of immune lymphocytes measured on syngeneic, allogeneic, and xenogeneic target cells, and the influence of protein A on cytotoxic activity in vitro suggest induction predominantly of natural killer cells in vivo which exhibit lytic activity on virus-infected target cells in vitro.

Vaccinia virus-specific CD8+ cytotoxic T lymphocytes in humans

“…CTL responses following infection with poxviruses have been documented in a number of species, including mice, rats, rabbits, and sheep (2,7,12,16,18,31). However, CTL responses to vaccinia virus have not been well characterized in nonhuman primates or in humans (22,26).…”

“…Cytotoxic activity peaked at 5 to 7 days postinfection and was present in T-cell-depleted but not in T-cell-enriched fractions. The investigators concluded that NK-like, not HLA-restricted, T-cell activity was generated in lymphoid organs of rhesus monkeys after vaccinia virus infection (26). Recently, Graham et al used UV-inactivated vaccinia virus-infected fibroblasts to stimulate immune PBMC in vitro to detect specific CTL responses in revaccinated humans, and no convincing vaccinia virus-specific CTL activity was observed (11).…”

“…Helper and cytotoxic T-cell responses following infection with poxviruses have been documented in a number of different animal species (2,5,12); however, the presence of CD4+ and CD8+ cytotoxic T lymphocytes (CTL) in vaccinia virus-immunized humans had not been demonstrated. Investigators at several laboratories have previously attempted to detect vaccinia virusspecific CTL responses in humans postimmunization but have reported negative results (11,22,26). Littaua et al, however, recently demonstrated that vaccinia virus-specific memory CD4+ CTL are present in vivo and could be cloned * Corresponding author.…”

Poxvirus pathogenesis.

“…CTL lyse virusinfected cells prior to virus maturation, thereby containing the spread of the infection within the host (521). The primary generation of poxvirus-specific CTL has been detected in many different species, including mice, rats, rabbits, and sheep, but not hamsters or primates (205,231,233,327,328,371,423,447,514,522). Although authentic human leukocyte antigen-restricted T cells specific for vaccinia virus have not previously been detected in the peripheral blood of primates (371,447), it is likely that with cell enrichment and isolation procedures currently available, one could isolate CTL clones.…”

Biological weapons

“…Earlier studies failed to detect vaccinia-specific cytotoxic T lymphocytes (CTLs) either in non-human primates or in humans [19][20][21], although poxvirus-specific CTLs were described in animal models [22,23]. Perrin et al advanced the hypothesis that non-T cytotoxic lymphocytes bearing Fc receptors and acting in the presence of specific antibodies were responsible for the vaccinia-virus cytotoxic activity observed in the PBMCs (peripheral blood mononuclear cells) of vaccinia-immune healthy humans [19].…”