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 (MΦ). It is now apparent that MΦ display remarkable plasticity in response to environmental signals to polarize into classically activated M(LPS + IFN-γ) or alternatively activated M(IL-4). However, little is known about how MΦ 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)-MΦ impacts direct presentation of viral antigens to influence effector and proliferative CD8+ T-cell responses. We show that M(IL-4) Sp-MΦ retain MHC-I surface expression and the ability to stimulate IFN-γ production by CTL following peptide stimulation and lymphocytic choriomeningitis virus infection to levels similar to M0 and M(LPS + IFN-γ) MΦ. However, memory CD8+ T cells cultured in the presence of M(IL-4) MΦ underwent significantly reduced proliferation and produced similar IFN-γ levels as coculturing with M0 or M(LPS + IFN-γ) cells. Thus, these results show a novel ability of polarized MΦ to regulate CD8+ T-cell proliferation and effector functions during virus infection.
Granulocyte/macrophage colony-stimulating factor (GM-CSF) and macrophage CSF (M-CSF) modulate differentiation and immune functions of macrophages (MF). Our aim was to evaluate how different MF differentiation conditions influence the MF response to virus infection. To address this, we differentiated bone marrow-derived MF in either GM-CSF or M-CSF and measured the cytokine responses to two different strains of lymphocytic choriomeningitis virus (LCMV) (clone 13; Cl13 or Armstrong; ARM). GM-CSF MF infected with either LCMV-ARM or -Cl13 produced more IL-6 than M-CSF MF, whereas M-CSF MF generated more IL-10 than GM-CSF MF. Interestingly, in M-CSF MF, LCMV-ARM induced more IL-10 production than Cl13. However, we could not detect any IL-12p70 or IL-23 after infection from either cell types. We also observed that GM-CSF MF was more efficient than M-CSF MF in supporting antigen-specific CD8 + T cell proliferation. Taken together, our data demonstrate that GM-CSF and M-CSF MF differ in how they respond to viral infection by their production of different cytokines, and their support for CD8 + T cell proliferation.
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