Search

Successful tumour immunity relies on innate and adaptive immune responses, with cytokines like interleukin 4 (IL-4) known to influence tumour clearance in both positive and negative ways. Here, we summarise some of the murine tumour models used over the past two decades to assess the impact of IL-4 on tumour immunity, with emphasis on the effects of IL-4 on the tumour-induced CD8 T-cell response. These data are compared with our own recent studies showing that IL-4 impairs CD8+ T-cell-mediated immunity against the mastocytoma cell line P815 expressing the immunogenic HLA-CW3 gene; moreover, we hypothesise that quantitative and qualitative differences in the HLA-CW3-induced CD8+ T-cell response impair control of tumour growth and aid the development of secondary tumours. We conclude that the duplicitous effects of IL-4 on tumour immunity depend on the type of effector cell (adaptive/innate) mediating tumour clearance and whether tumour growth depends on stromal infrastructure. Thus, the search for factors that improve or weaken the effectiveness of tumour-specific T cells has to be continued to improve modern approaches of immunotherapy against cancer. [ABSTRACT FROM AUTHOR]

Mice susceptible and resistant to murine cytomegalovirus (MCMV) were infected with this virus and livers were harvested after 2-231 days. Cryostat sections were stained to visualize cells bearing CD4, CDS or Mac-1 antigens. Mac-1+ cells were prevalent in inflammatory foci after 2 days. These cells persisted in susceptible BALB/c and A/J mice, but disappeared from livers of resistant C57B1/ 6 and CBA/CaH mice by day 28. T cell inflammation peaked on days 7-11. This declined by day 56 in C57B1/6 and CBA/CaH mice, but persisted in BALB/e and A/J mice for at least 231 days. Persistent CD8+ cells were dispersed throughout the parenchyma. More CD8+ cells were observed 7-14 days after infection in the livers of bg/bg (natural killer (NK) cell-deficient) C57B1/6 and CBA mice, and in C57B1/6 mice depleted of NK 1.1 cells by MoAb. Thus, mice of strains susceptible to MCMV exhibit hepatitis characterized by persistence of dispersed CD8+ cells. This phenomenon may be limited by NK cells in resistant strains. [ABSTRACT FROM AUTHOR]

The roles of the inflammatory cytokines tumour necrosis factor-α (TNF-α), interleukin-1 (IL-1) and IL-12, in murine cytomegalovirus (MCMV) disease were investigated in susceptible BALB/c and resistant C57BL/6 mice. MCMV infection induced IL-1 and TNF-α production by peritoneal cells from BALB/c mice, as demonstrated previously in C57BL/6 mice. Overt ill-health and viral replication in the spleens of BALB/c mice were increased by in vivo treatment with soluble TNFα receptors to inhibit the activity of this cytokine, whilst antibodies to IL-12 had a similar but more restricted effect. C57BL/6 mice were not affected by either treatment, suggesting TNF-α and IL-12 are not critical for natural killer cell-mediated restriction of viral replication in the spleen. Soluble TNF-α receptors and antibodies to IL-12 also enhanced MCMV titres and numbers of viral antigen-positive cells in the livers of BALB/c mice and TNF-α receptors have similar effects in C57BL/6 livers. In contrast, IL-1 receptors improved the health of MCMV-infected BALB/c mice and reduced viral replication and hepatitis at some time-points. Mechanisms which may underlie these changes are discussed. [ABSTRACT FROM AUTHOR]