Fc gamma receptor I (CD64)-negative human monocytes are potent accessory cells in viral antigen-induced T cell activation and exhibit high IFN-alpha-producing capacity

Blood monocytes represent a heterogeneous cell population with respect to phenotype and function. We have previously described that a minor subset of Fc gamma 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)-alpha within human monocytes. In the present study we demonstrate that CD64(-) monocytes are also the main producers of IFN-alpha in response to Herpes simplex virus type 1 (HSV-1) or influenza (type A) antigens. The virus-induced IFN-alpha 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-alpha 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-gamma 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.