Antigen-laden cells in thoracic duct lymph. Implications for adoptive transfer experiments

Abstract

T cells from thoracic duct lymph of donor rats suppress the adoptive secondary response to human serum albumin (HSA). The original aim of the present investigation was to determine whether these non-immune cells have antigen-specific receptors. Thoracic duct lymphocytes (TDL) were depleted in vivo of antigen-specific T cells (negatively selected) by acutely injecting non-immune donors with HSA at the time of thoracic duct cannulation. Negatively selected TDL were mixed with memory cells (primed TDL from previously immunized donors) and transferred into irradiated recipients to assess whether the suppressive potential had disappeared. Paradoxically, the addition of negatively selected TDL (which were unresponsive to HSA) augmented the adoptive secondary anti-HSA response. Further study showed that the augmented response was mediated by a very small number of cells (∼ 1 in 5000) laden with antigen that appeared in lymph of non-immune donors following HSA injection. These antigen-bearing cells were highly immunogenic and furthermore could overcome the effects of T suppressor cells in vivo. Once antigen laden cells were removed from lymph (by affinity chromatography), however, negatively selected TDL were found to inhibit the adoptive secondary response suggesting that either suppression in this model is non-specific or that antigen-specific suppressor cells are not selected out of the recirculating pool by antigen.