Selection of the delayed hypersensitivity T effector and T suppressor cell response by antigen-presenting macrophages

The T effector lymphocytes of delayed type hypersensitivity reactions (TDH) are regulated by a complex T suppressor (Ts) cell circuit. Induction of TDH cells requires Ia+ adherent cells as antigen-presenting cells. Little is known about the antigen presentation of the induction of Ts cells. We describe an experimental model in which TDH and Ts cells are induced separately by different antigen-presenting macrophages grown from bone marrow stem cells. Bone marrow derived macrophages grown in L cell-conditioned medium for various periods and labeled with 2,4-dinitrobenzene sulfonic acid differ in their ability to induce TDH and Ts cells in vitro. The functional activity of the two T subpopulations was assessed in vivo by epicutaneous challenge or sensitization with 2,4-dinitrofluorobenzene of mice receiving the in vitro educated cells. Ear swelling or suppression of swelling was recorded. It could be shown that 5-7 day bone marrow-derived DNP-labeled macrophages preferentially induced Thy 1+ Lyt 1+ antigen-specific TDH cells; 7-10 day old antigen-presenting bone marrow-derived macrophages induced preferentially Thy 1+ Lyt 2+ antigen specific Ts cells. Characterization of various phenotypic markers revealed different surface antigen expression and functional differences such as MIF responsiveness or transglutaminase activity on the two macrophage populations. These data support the concept that activation of the Ts regulatory circuit may require antigen presentation by specialized antigen presenting cells, characterized by certain surface and functional markers and different from those inducing preferentially TDH cells.