Fas (CD95)/Fas ligand interactions regulate antigen-specific, major histocompatibility complex-restricted T/B cell proliferative responses.
The effect of Fas ligand (FasL) cytotoxicity on T/B collaboration was examined in vitro using cloned T helper 1 cells and antigen-pulsed, activated B cells. We compared antigen-pulsed B cells that had been activated through different membrane receptors (IgM, CD14 and CD40) for their ability to induce T cell proliferation and to respond to T cell help. We also used a Fas-Ig fusion protein, an inhibitor of FasL-mediated cytotoxicity, to determine the effect of FasL cytotoxicity on the T and B cell proliferative responses. The data show that the extent of both T and B cell proliferative responses correlate with the relative resistance of activated B cell populations to FasL cytotoxicity. Moreover, both T and B cell proliferation could be enhanced by Fas-Ig. Our results demonstrate that FasL cytotoxicity is a negative regulatory mechanism for both T and B cell proliferative responses and that Fas-Ig can be an immunopotentiating agent for both T and B cell immunity.
Ozdemirli
M
M
Arthritis Center, Department of Pathology, Boston University School of Medicine, MA 02118, USA.
El-Khatib
M
M
Foote
L C
LC
Wang
J K
JK
Marshak-Rothstein
A
A
Rothstein
T L
TL
Ju
S T
ST
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology; D000939:Epitopes / Q000187:drug effects / Q000276:immunology*; D053222:Fas Ligand Protein; D007136:Immunoglobulins / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D008211:Lymphocyte Cooperation / Q000235:genetics; D008285:Major Histocompatibility Complex / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D019014:fas Receptor / Q000494:pharmacology*
D000939:Epitopes; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007136:Immunoglobulins; D008024:Ligands; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D019014:fas Receptor