M(IL-4) Tissue Macrophages Support Efficient Interferon-Gamma Production in Antigen-Specific CD8+ T Cells with Reduced Proliferative Capacity

CD8(+) cytotoxic T cell (CTL) responses are necessary for the lysis of virally infected cells and control of infection. CTLs are activated when their TCRs bind a major histocompatibility complex (MHC)-I/peptide complex on the surface of antigen presenting cells such as macrophages (M Phi). It is now apparent that M Phi display remarkable plasticity in response to environmental signals to polarize into classically activated M(LPS + IFN-gamma) or alternatively activated M(IL-4). However, little is known about how M Phi activation status influences their antigen presentation function to CD8(+) T cell in models of virus infection. Consequently, we tested how polarization of spleen-derived (Sp)-M Phi impacts direct presentation of viral antigens to influence effector and proliferative CD8(+) T-cell responses. We show that M(IL-4) Sp-M Phi retain MHC-I surface expression and the ability to stimulate IFN-gamma production by CTL following peptide stimulation and lymphocytic choriomeningitis virus infection to levels similar to M0 and M(LPS + IFN-gamma) M Phi. However, memory CD8(+) T cells cultured in the presence of M(IL-4) M Phi underwent significantly reduced proliferation and produced similar IFN-gamma levels as coculturing with M0 or M(LPS + IFN-gamma) cells. Thus, these results show a novel ability of polarized M Phi to regulate CD8(+) T-cell proliferation and effector functions during virus infection.