Phenotypic and functional characterization of human suppressor T-cell clones: II. Activation by Mycobacterium leprae presented by HLA-DR molecules to alpha beta T-cell receptors.
We have been studying human T-cell clones that suppress anti-mycobacterial T-cell responses but not T-cell responses to an unrelated antigen or mitogen. In the present paper we report our studies on the activation requirements of these suppressor-T-cell clones. The suppressor-T-cell clones could proliferate and produce interferon-gamma upon stimulation with Mycobacterium leprae and other mycobacteria but not with unrelated antigens or autologous T cells. Both suppressor and nonsuppressor clones react to a 36-kDa antigen of M. leprae. Thus far, we have not been able to demonstrate whether they see the same or different epitopes. The antigen-driven proliferation of suppressor-T-cell clones was, however, significantly lower than that observed for T-cell clones that did not mediate suppression. The proliferation of suppressor-T-cell clones to M. leprae antigens could be blocked by monoclonal antibodies to HLA-DR, alpha beta T-cell receptor, interleukin-2 receptor, and, in the case of CD4-positive suppressor-T-cell clones, anti-CD4 monoclonal antibodies. DR restriction of the antigen presentation to these suppressor-T-cell clones was shown in mixing experiments using antigen-presenting cells as mononuclear cells from family members and unrelated individuals. These experiments also indicated that apart from regular DR-restriction a hitherto unknown factor may be required for presentation to or activation of suppressor-T-cell clones that is present in the family members and unrelated individuals with the same ethnic and geographic background but absent in DR/Dw-matched healthy Dutch individuals.
Department of Immunohaematology and Blood Bank, University Hospital, Leiden, The Netherlands.
S G
SG
Li
D G
DG
Elferink
R R
RR
de Vries
D000911:Antibodies, Monoclonal; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells; D000939:Epitopes / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000494:pharmacology; D015439:Leprosy, Borderline / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D009166:Mycobacterium leprae / Q000276:immunology*; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D015704:CD4 Antigens; D000939:Epitopes; D006684:HLA-DR Antigens; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma