Thymomodulin increases HLA-DR expression by macrophages but not T-lymphocyte proliferation in autologous mixed leucocyte reaction

Thymomodulin (TMD), a thymic biological response modifier, stimulates the release of tumour necrosis factor (TNF) and granulocyte-macrophage-colony stimulating factor (GM-CSF) in macrophage-lymphocyte cultures. We investigated the effects of the cytokines released in cultures with TMD, on the expression of human leucocyte antigen-DR (HLA-DR) antigens by alveolar macrophages (AM) and the T-cell proliferation induced in autologous mixed leucocyte reaction (AMLR) cultures or by T-cell mitogens. Among freshly isolated AM, 84 ± 4% were HLA-DR positive, and this proportion was significantly reduced after 24 h cultures (60 ± 3%, p <0.05). In cultures without peripheral blood (PBL) lymphocytes, TMD did not change HLA-DR expression by AM CHLA-DR + AM; whilst in the presence of autologous PBL lymphocytes, TMD induced an increase in the proportions of HLA-DR + AM (TMD 100 μg · ml^-1 79 + 3%, p <0.04 vs control cultures). However, TMD did not change the ability of AM to induce T-cell proliferation in AMLR between AM and PBL lymphocytes. In contrast, in PBL mononuclear cell cultures, TMD induced a further increase of the cell proliferation due to the T-cell mitogens interleukin-2 (IL-2) or phytohaemagglutinin (PHA) (p <0.05 vs each control culture with mitogens) or anti-CD3 antibodies (p <0.03 vs control cultures). Thus, the cytokines released in cultures with TMD enhance macrophage HLA-DR expression. Whilst this phenomenon is not associated with changes in the ability of AM to stimulate T-cell proliferation, TMD is able to increase the mitogen-induced T-cell proliferation.