Importance of HLA-D antigens for the cooperation between human monocytes and T lymphocytes.

The ability of autologous and allogeneic monocytes to restore the responsiveness of purified T lymphocytes to tuberculin (PPD) was studied in twelve different experiments involving eleven unrelated T lymphocyte donors and a large number of related and unrelated monocyte donors. T lymphocyte suspensions were prepared by passage of peripheral blood mononuclear cell suspensions through Ig-anti-Ig-coated columns. Monocyte-enriched suspensions were prepared from mononuclear suspensions by density gradient centrifugation on albumin solution and added to the T cell suspension in a final concentration of 3%. Autologous monocytes and monocytes from related donors sharing one HLA haplotype with the T cell donor partly restored the responsiveness to PPD, and so did monocytes from unrelated donors who shared HLA-D alleles with the T cells. None of eight monocyte suspensions from eight unrelated donors sharing no HLA-D antigens with the T cell donor were able to restore the responsiveness to PPD. The difference between HLA-D-sharing and nonsharing monocytes could not be explained by a simultaneous allogeneic reaction, as the addition of monocytes autologous with the T cells to mixtures of non-HLA-D-sharing T cells and monocytes partly restored the response. Moreover, experiments with the addition of PPD to ordinary mixed leukocyte cultures revealed only a moderate depression on the PPD response. It is concluded that in man – as in mice and guinea pigs – some HLA-D identity between monocytes and T lymphocytes is necessary for a cooperation to take place in the secondary immune response. This observation emphasizes the homology between HLA-D antigens in man and Ia antigens in animals.