Selective DNAM-1 expression on small peritoneal macrophages contributes to CD4⁺ T cell costimulation

Mouse peritoneal macrophages consist of two subsets: large peritoneal macrophages (LPMs) and small peritoneal macrophages (SPMs), defined as CD11b^hiF4/80^hi and CD11b⁺F4/80^lo cells, respectively. We reveal that SPMs, but not LPMs, have the ability to present antigens to naïve CD4⁺ T cells. Coculture of SPMs with naïve ovalbumin (OVA) specific CD4⁺ T cells (OT-II) in the presence of OVA peptide effectively induced CD4⁺ T cells priming. SPMs, but not LPMs, strongly express DNAM-1, an activating immunoreceptor. Although antigen uptake and processing were comparable between WT and DNAM-1-deficient SPMs, deficiency of DNAM-1 on SPMs or blockade of DNAM-1 and its ligand interaction impaired CD4⁺ T cells priming by SPMs. Furthermore, T and B cell responses in mediastinal lymph nodes of mice intraperitoneally immunized with trinitrophenyl (TNP)-OVA protein in Alum adjuvant were enhanced by intraperitoneally transferred wild-type, but not DNAM-1-deficient, SPMs. We propose that SPMs are functionally distinct from LPMs, and DNAM-1 plays a costimulatory role in antigen presentation by SPMs.