Fcγ receptor I (CD64)‐negative human monocytes are potent accessory cells in viral antigen‐induced T cell activation and exhibit high IFN‐α‐producing capacity

Blood monocytes represent a heterogeneous cell population with respect to phenotype and function. We have previously described that a minor subset of Fcγ receptor I‐negative (CD64 ‐ ) monocytes, comprising < 10% of all monocytes, exhibits a significantly higher accessory capacity in allogeneic or purified protein derivative (PPD) of tuberculin‐induced T cell activation than the majority of CD64‐expressing (CD64 + ) monocytes. CD64 ‐ monocytes were also found to represent the major source of Newcastle disease virus (NDV)‐induced interferon (IFN)‐α within human monocytes. In the present study we demonstrate that CD64 ‐ monocytes are also the main producers of IFN‐α in response to Herpes simplex virus type 1 (HSV‐1) or influenza (type A) antigens. The virus‐induced IFN‐α release by monocytes, but mainly that by CD64 ‐ monocytes, can be further increased by co‐culture with autologous T cells, which alone do not produce significant amounts of IFN‐α in response to virus. In addition, CD64 ‐ and CD64 + monocytes also differ in their accessory capacity in virus‐induced T cell responses. CD64 ‐ monocytes exposed to influenza antigens induced higher IFN‐γ release and proliferation by the responding autologous T cells than virus‐exposed CD64 + monocytes. In virus‐stimulated monocyte/T cell co‐cultures, CD64 ‐ monoyctes also induced larger size cell clusters than CD64 + monocytes, indicating direct cell‐to‐cell interaction with a higher number of T cells, which represent the main component of these clusters. J. Leukoc. Biol . 60: 389–396; 1996.