In vitro effects of solubilized HLA-DR--role in immunoregulation?

To test the hypothesis that soluble HLA-DR antigens (sHLA-DR), binding to the T-cell receptor (TCR) and/or CD4 structures, compete with and abrogate functions of their cell-bound counterparts, we studied effects of detergent-solubilized, affinity-purified HLA-DR molecules on the DNA synthesis, IL-2, and IL-1 secretion by human peripheral blood mononuclear cells (PBMC). While resting T cells did not show any response, there was a dose-dependent suppression of T-cell responses induced by mitogen (phytohemagglutinin, PHA), recall antigen (purified protein derivative of tuberculin, PPD), or HLA class II alloantigens (Daudi cells). In the PHA system, sHLA-DR affected DR-identical and DR-disparate PBMC with equal efficiency, suggesting a nonspecific interference with accessory functions of cell-bound HLA class II molecules.

Are soluble monocyte-derived HLA class II molecules candidates for immunosuppressive activity?

Supernatants of human blood monocyte cultures suppressed PHA responses (IL-2 synthesis, IL-2R expression, DNA synthesis) of autologous and allogeneic lymphocytes. The main suppressive activity was found in the 65-kDa (and 23-kDa) range. It could be incompletely neutralized by mAb specific for a non-polymorphic HLA DR determinant and could also be adsorbed to and eluted from an anti-DR immunoabsorbent column.

The so-called interleukin-2 inhibitory activity of human serum is largely cytotoxic to mouse cells.

No specific interleukin-2 (IL-2) inhibitor has ever been demonstrated in human, mouse, or any other animal serum. Native mouse serum contains activities which completely inhibit IL-2-dependent and IL-2-independent in vitro proliferation of cells of different animal species by a non-cytotoxic mechanism. The decisive inhibitory component of mouse serum has a molecular weight of about 80,000, is heat-labile and has not been found in other animal sera.

[Clinical value of interleukin 1- and interleukin 2-determinations in patients after kidney transplantation].

In a retrospective study of allograft rejections in renal transplant recipients we examined the value of cytokine production monitoring. Interleukin 1 (IL 1) and interleukin 2 (IL 2) activities were determined in supernatants of mitogen-stimulated peripheral blood lymphocytes in 8 renal transplant recipients serially for a period up to 60 days after transplantation. LPS-induced IL 1 as well as PHA-induced IL 2 production in patients after renal transplantation were significantly decreased in comparison to healthy controls.

[Interleukins 1-8].

Interleukins are well defined biologically active factors serving the intercellular communication. Here is given a review on the interleukins 1-8.