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 micrograms.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.
Balbi
B
B
Interuniversitary Center for Lung Diseases of Northern Italy, Milan.
Valle
M T
MT
Oddera
S
S
Manca
F
F
Rossi
G A
GA
Allegra
L
L
D000328:Adult; D000704:Analysis of Variance; D000954:Antigens, Surface / Q000032:analysis / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis / Q000187:drug effects*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology; D007959:Lymphocyte Culture Test, Mixed; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013268:Stimulation, Chemical; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D013949:Thymus Extracts / Q000494:pharmacology*
D000954:Antigens, Surface; D006684:HLA-DR Antigens; D013949:Thymus Extracts; C051006:thymomodulin