Functional similarity and differences between selection-independent CD4-CD8- alphabeta T cells and positively selected CD8 T cells expressing the same TCR and the induction of anergy in CD4-CD8- alphabeta T cells in antigen-expressing mice.
In TCR-alphabeta transgenic mice, CD4-CD8- TCR-alphabeta+ (alphabeta DN) cells arise in the absence of positively selecting MHC molecules and are resistant to clonal deletion in Ag-expressing mice. In this study the activation requirements and functional properties of alphabeta double-negative (DN) cells were compared with those of positively selected CD8+ cells expressing equivalent levels of the same MHC class I-restricted transgenic TCR. We found that positively selected CD8+ cells required a lower density of the antigenic ligand for optimal proliferative responses compared with alphabeta DN cells derived from nonpositively selecting mice. However, when the CD8 coreceptor on CD8+ cells was blocked with an anti-CD8 mAb, both alphabeta DN and CD8+ cells exhibited the same dose-response curve to the antigenic ligand and the same dependence on CD28/B7 costimulation. Positively selected CD8+ cells also differed from alphabeta DN cells in that they differentiated into more efficient killers and IL-2 producers after Ag stimulation, even after CD8 blockade. However, Ag-activated alphabeta DN and CD8+ cells were equally efficient in producing IFN-gamma, suggesting that this functional property is independent of positive selection. We also found that alphabeta DN cells recovered from the lymph nodes of Ag-expressing mice were functionally anergic. This anergic state was associated with defective proliferation and IL-2 production in response to Ag stimulation. These observations indicate that alphabeta DN cells can be anergized in vivo by physiological levels of the antigenic ligand.
Caveno
J
J
Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
Zhang
Y
Y
Motyka
B
B
Teh
S J
SJ
Teh
H S
HS
D000818:Animals; D000941:Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015704:CD4 Antigens / Q000096:biosynthesis / Q000235:genetics*; D016827:CD8 Antigens / Q000096:biosynthesis / Q000235:genetics*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D017635:Clonal Anergy / Q000235:genetics* / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D005260:Female; D006183:H-2 Antigens / Q000235:genetics; D006182:H-Y Antigen / Q000276:immunology; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000235:genetics; D008222:Lymphokines / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D011485:Protein Binding / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D000941:Antigens; D015704:CD4 Antigens; D016827:CD8 Antigens; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D006182:H-Y Antigen; D018960:Hyaluronan Receptors; D008222:Lymphokines; D016693:Receptors, Antigen, T-Cell, alpha-beta; D017493:Leukocyte Common Antigens