Immunoregulatory Adherent Cells in Human Tuberculosis: Radiation-Sensitive Antigen-Specific Suppression by Monocytes

Abstract

In human tuberculosis, adherent mononuclear cells (AMC) selectively depress in vitro responses to the mycobacterial antigen tuberculin purified protein derivative (PPD). The phenotype of this antigen-specific adherent suppressor cell was characterized by examining the functional activity of adherent cells after selective depletion of sheep erythrocyte-rosetting T cells or OKMI-reactive monocytes, Adherent cell suppression was studied in the [³H]thymidine-incorporation microculture assay by using T cells rigorously depleted of T cells with surface receptors for the Fe portion of IgG (Tγ cells) as antigen-responsive cells. PPD-induced [³H]thymidine incorporation by these nony T cellswas uniformly reduced (mean, 42% ± 10% [SD]) when autologous AMC were added to nony T cells at a ratio of 1:2. Antigen-specific suppression by AMC was not altered by depletion of sheep erythrocyte-resetting T cells or treatment with indomethacin. However, AMC treated with OKMI and complement or γ irradiation (1,500 rads) no longer suppressed tuberculin responses in vitro. These studies identify the antigen-specific adherent suppressor cell in tuberculosis as an OKMI-reactive, non-erythrocyte-resetting monocyte. The radiosensitivity of this monocyte immunoregulatory function may facilitate its further definition.