Modulation of antigen-induced T cell proliferation by alpha 2M-trypsin complexes.
Proteinase-complexed alpha 2-macroglobulin (alpha 2M) could be shown to interfere with T cell proliferation in response to antigen presented by autologous antigen-pulsed monocytes (M phi) (antigen-induced M phi-T cell interaction, MTI). Addition of alpha 2M-trypsin (alpha 2M X T) complexes to cultures of T cells and antigen-pulsed M phi led to a dose-dependent decrease of T cell proliferation (up to 91% inhibition of the T cell response), whereas the same concentrations of free (native) alpha 2M had no effect on antigen-induced MTI. The observed interference with MTI could be attributed to residual enzymic activity of the alpha 2M X T complex. Addition of aprotinin, a low Mr protein proteinase inhibitor able to penetrate to the enzyme entrapped within the alpha 2M molecule and thus bind to and inactivate the enzyme's active site, resulted in a reversal of the alpha 2M X T-induced biological effect. Inactivation of the enzyme's active site within alpha 2M X T was monitored by a decrease in the hydrolytic activity of the complex. Kinetic studies (addition of alpha 2M X T 24 to 48 hr after culture onset was shown to be still inhibitory) indicated an effect at the level of the T cell or its mediators, but an overnight incubation of T cells with alpha 2M X T did not alter these cells' capacity to proliferate in response to an antigenic stimulus. An additional effect of alpha 2M X T on the antigen-presenting cell cannot be ruled out at present. However, alpha 2M X T did not alter the percentage of monocytes expressing HLA-DR, -DP, and -DQ or interfere with interleukin 1 release if added to M phi at concentrations that significantly inhibited MTI. Furthermore, incubation of M phi with alpha 2M X T for 1 hr before antigen pulsing had no effect on the M phi antigen presenting capacity.
J W
JW
Mannhalter
W
W
Borth
M M
MM
Eibl
D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D000942:Antigens, Bacterial / Q000276:immunology*; D007611:Aprotinin / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007166:Immunosuppressive Agents / Q000276:immunology / Q000494:pharmacology*; D007375:Interleukin-1 / Q000378:metabolism; D007525:Isoelectric Focusing; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D009000:Monocytes / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D014357:Trypsin / Q000276:immunology / Q000494:pharmacology*; D000511:alpha-Macroglobulins / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*
D000942:Antigens, Bacterial; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D007375:Interleukin-1; C028939:alpha-2-macroglobulin-trypsin complex; D000511:alpha-Macroglobulins; D007611:Aprotinin; D014357:Trypsin