Alveolar Macrophages. VI. Regulation of Alveolar Macrophage-mediated Suppression of Lymphocyte Proliferation by a Putative T Cell

Alveolar macrophages (AM) from normal rats suppressed antigen- or mitogen-stimulated blastogenic responses in cultures of splenic or lymph node lymphocytes, high levels of suppression often being observed when added AM comprised as few 0.6% of the total cells in culture. The efficiency of AM-mediated suppression of spleen cell blastogenesis declined with the age of the spleen cell donors, was severely curtailed by pretreatment of donors with low levels of cyclophosphamide, and was depleted by adult thymectomy coupled with thoracic duct drainage. The suppressive activity of AM was most obvious at high cell density, was unaffected by the presence of indomethacin in the cultures, or by prior X-irradiation of the spleen cells. Fractionation of spleen cells by velocity sedimentation yielded cell populations of greatly varying sensitivities to AM-mediated suppression, from small splenocytes (sedimentation velocity 1.1-2.8 mm/h) which were almost totally refractory to AM-suppression when assayed in isolation from the remainder of the spleen cell population, to larger cells (sedimentation velocity greater than 3.,5 mm/h) exhibiting high levels of sensitivity. Fractionation of spleen cells by glass wool adherence indicated decreased sensitivity to AM-suppression in the effluent population. Examination of the suppressive activity of individual subpopulations of AM separated by velocity sedimentation indicated that the larger macrophages were the most active in vitro. Suppressive activity of this nature was not seen with unstimulated peritoneal macrophages, but was observed when 'activated' peritoneal exudate cells were tested. These data are discussed in terms of a two-cell model for suppression of blastogenesis, the ultimate effector cell being a macrophage, the activity of which is controlled by a long-lived, recirculating lymphocyte, which we have provisionally designated as a T lymphocyte.