Macrophage colony-stimulating factor can modulate immune responses and attract dendritic cells in vivo

Studies have indicated that professional APCs in the periphery, such as den dritic cells and macrophages, play an important role in initiating DNA vacc ine-specific immune responses. To engineer the immune response induced by D NA vaccines in vivo we investigated the modulatory effects of codelivering growth factor genes for the hematopoietic APCs along with DNA vaccines. Spe cifically, we examined the effects on the antigen-specific immune responses following the codelivery of the gene expression cassettes for M-CSF, G-CSF , and GM-CSF along with HIV-1 DNA immunogen constructs. We observed that co immunization with GM-CSF increased the antibody response and resulted in a significant enhancement of lymphoproliferative response. Furthermore, among all coinjection combinations, we found that M-CSF coinjections resulted in a high level of CTL enhancement. This enhancement of CTL responses observe d from the coinjection with M-CSF was CD8(+) T cell dependent and was assoc iated with the presence of CD11c(+) cells at the site of injection and with the antigen-specific induction of the beta-chemokine MIP-1 beta, suggestin g a role for this chemokine in CTL induction. These results suggest that he matopoietic growth factors should be further studied as potential adjuvants for in vivo modulators of immune responses.