Immune recognition of tumor cells in mice infected with Pichinde virus

Abstract

Pichinde virus (PV), a member of the Arenaviridae family, protects mice from a lethal inoculation with the sarcoma 180 (S180) tumor cell line. Virus replication, which is required for protection, occurs primarily in the spleen and tumor. During the first 4 days, elevated natural killer (NK) cell activity parallels an increase in serum interferon in PV-infected mice. On day 7 after infection virus-specific cytotoxic T cells (CTLs) are found in the mouse. This strong response peaks on day 13 and gradually declines over the next 17 days. The tumor-specific CTL response appears more slowly and is less intense than the virus-specific response, especially in the uninfected mouse. However, CTLs from either type of mouse recognize PV-infected tissue culture S180 target cells better than uninfected ones. Even though the primary tumor-specific immune response appears weak, mice that have cleared both virus and tumor are refractory to a subsequent challenge with S180 cells and rapidly produce tumor-specific CTLs. Thus, our data indicate a number of ways in which virus infection could lead to immune elimination of tumors: (1) Virus-induced interferon stimulates NK-cell activity, which in turn could control tumor load until a specific response is mounted against the S180 cells; (2) early onset of the tumor-specific T-cell response could be brought about by viral-enhanced tumor antigen presentation to the immune system; and (3) the tumor-specific T-cell response could be augmented through a "bystander' phenomenon involving factors associated with T cells responding specifically and vigorously to the virus itself.

Allogeneic H-2 antigen expression is insufficient for tumor rejection.

“…Only one early study describes the growth of Sal in certain allogeneic tumor recipients. The absence of strain specificity in these studies was only seen, however, when mice were challenged with Sal cells grown in donors who had been pretreated with large quantities of tumor or normal tissue extracts (40). Therefore, under normal tumor challenge conditions, the Sal tumor behaves as expected for an allograft and follows the (Fig.…”

Disruption of Murine Cardiac Allograft Acceptance by Latent Cytomegalovirus

“…Exogenous type I interferons have been linked with clinical allograft rejection (54-57), accelerated cardiac rejection in rodents (58), and recently disruption of tolerance and graft acceptance in several different models (59-61). If MCMV is reactivating and acutely infecting naïve allografts, it becomes similar to other acute viral infections that induce IFN-α and disrupt allograft acceptance, such as lymphocytic choriomeningitis virus and Pichinde virus (6-8, 62-64). IFN-α directly stimulates murine NK-cells to expand, become cytotoxic, and release both TNF-α and IFN-γ (49, 65, 66), as well as non-specifically stimulate bystander T cells (67).…”

Antibody to mouse alpha/beta interferon abrogates Pichinde virus-induced liver lesions in suckling mice

“…At 8 days after injection, two litters in each group were sacrificed for histologic examination of the livers. At 5 and 10 days after injections, two litters in each experimental group were sacrificed, and the livers were assayed for virus as previously described (12). The mean cumulative weight increase for uninfected mice injected with antibody to IFN-a/p was 5.3 ± 0.3 g after 10 days.…”