Cytolytic mechanisms and expression of activation-regulating receptors on effector-type CD8+CD45RA+CD27- human T cells.
Circulating CD8+ T cells with a CD45RA+CD27- phenotype resemble cytolytic effector cells because they express various cytolytic mediators and are able to execute cytotoxicity without prior stimulation in vitro. We here demonstrate that CD8+CD45RA+CD27- T cells can use both granule exocytosis and Fas/Fas ligand pathways to induce apoptosis in target cells. The availability of these cytolytic mechanisms in circulating T cells suggests that the activity of these cells must be carefully controlled to prevent unwanted tissue damage. For this reason, we analyzed the expression of surface receptors that either enhance or inhibit T cell function. Compared with memory-type cells, effector cells were found to express normal levels of CD3epsilon and TCRzeta and relatively high levels of CD8. CTLA-4 was absent from freshly isolated effector cells, whereas a limited number of unstimulated memory cells expressed this molecule. In line with recent findings on CD8+CD28- T cells, CD45RA+CD27- T cells were unique in the abundant expression of NK cell-inhibitory receptors, both of Ig superfamily and C-type lectin classes. Binding of NK cell-inhibitory receptors to classical and nonclassical MHC class I molecules may inhibit the activation of the cytolytic machinery induced by either Ag receptor-specific or nonspecific signals in CD8+CD45RA+CD27- T cells.
Department of Immunobiology and Laboratory for Experimental and Clinical Immunology, Academic Medical Center, CLB, University of Amsterdam, Amsterdam, The Netherlands.
P A
PA
Baars
L M
LM
Ribeiro Do Couto
J H
JH
Leusen
B
B
Hooibrink
T W
TW
Kuijpers
S M
SM
Lens
R A
RA
van Lier
D000069594:Abatacept; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D060908:CTLA-4 Antigen; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D005089:Exocytosis / Q000276:immunology; D006801:Humans; D018796:Immunoconjugates; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000096:biosynthesis* / Q000097:blood; D008213:Lymphocyte Activation / Q000276:immunology*; D008565:Membrane Proteins / Q000096:biosynthesis; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis* / Q000502:physiology; D011971:Receptors, Immunologic / Q000096:biosynthesis; D054340:Receptors, KIR; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis* / Q000097:blood
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C054979:antigen T cell receptor, zeta chain; D000069594:Abatacept; D017493:Leukocyte Common Antigens