Viral induction of co-stimulatory activity on antigen-presenting cells bypasses the need for CD4+ T-cell help in CD8+ T-cell responses

Abstract

Background: CD4+ T-cell help is critical for cytotoxic (CD8+) T-lymphocyte responses to many antigens, such as viruses, minor histocompatibility antigens and allogeneic major histocompatibility antigens. However, the nature of such help is still a mystery: cytokines such as interleukin-2 may be involved but cell-cell contact may also be necessary. As some viruses can induce CD8+ T-cell responses in the absence of CD4+ T cells, we asked whether these viruses and CD4+ cells share a pathway for helping the CD8+ T-cell response.

Results: We show here that the H2N2 subtype of influenza virus, which elicits a CD4+ T-cell-independent anti-viral CD8+ T-cell response in vitro, induces expression of the co-stimulatory molecule B7-2, but not of B7, on the cell surface of antigen-presenting cells. In contrast, the H1N1 subtype of influenza virus, which requires CD4+ T-cell help to elicit CD8+ T-cell responses under the same conditions, does not induce B7-2 expression. We also find that CD4+ T cells can induce expression of B7-2 on antigen-presenting cells. In both cases, the induced B7-2 is necessary for the clonal expansion and functional maturation of CD8+ T cells.

Conclusion: Our results support the view that the induction of co-stimulatory activity on antigen-presenting cells by CD4+ T cells can substitute for the requirement for exogenous interleukin-2 in CD8+ T-cell help. Viruses that can induce co-stimulatory activity on antigen-presenting cells thus induce a CD4+ T-cell-independent CD8+ T-cell response. These findings could explain the reported differences in the requirements for CD4+ T cells in CD8+ T-cell responses.