Human autoreactive CD4+ T cell clones use perforin- or Fas/Fas ligand-mediated pathways for target cell lysis.
It is well established that target cell lysis by MHC class I-restricted CD8+ T cells is an important defense mechanism during infections with intracellular pathogens or against tumor targets. On the other hand, little is known about the physiologic role and the mechanisms of cytotoxicity of CD4+ MHC class II-restricted T cells. We have recently demonstrated that human autoreactive CD4+ T cells specific for one candidate autoantigen of multiple sclerosis, myelin basic protein, can mediate cytotoxicity. In the present report, we analyze the cytolytic mechanisms employed by these cells. We show that individual T cell clones, regardless of their cytokine phenotype, can be noncytotoxic or lyse target cells via either perforin- or Fas/Fas ligand-mediated cytotoxicity.
Vergelli
M
M
Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA.
Hemmer
B
B
Muraro
P A
PA
Tranquill
L
L
Biddison
W E
WE
Sarin
A
A
McFarland
H F
HF
Martin
R
R
D001324:Autoantigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein; D053804:Granzymes; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology*; D004676:Myelin Basic Protein / Q000276:immunology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012697:Serine Endopeptidases / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology / Q000276:immunology; D019014:fas Receptor / Q000502:physiology*
D001324:Autoantigens; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D004676:Myelin Basic Protein; D052899:Pore Forming Cytotoxic Proteins; D019014:fas Receptor; D054353:Perforin; D015847:Interleukin-4; D007371:Interferon-gamma; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human