Cutting edge: the NK cell receptor 2B4 augments antigen-specific T cell cytotoxicity through CD48 ligation on neighboring T cells.
2B4 is expressed on all NK and a subset of memory/effector CD8(+) T cells. 2B4 binds to CD48 and activates NK cytotoxicity, but its function on CD8(+) T cells is not clear. Furthermore, two isoforms of 2B4 (2B4S and 2B4L) exist in mice but the role of individual isoforms is not known. To address these questions, we generated primary T cell cultures from L(d)-specific 2C/Rag2(-/-) TCR transgenic mice and transduced them with 2B4S or 2B4L. 2B4S- or 2B4L-transduced T cells showed greater cytotoxicity over control cells against CD48(+) and CD48(-) targets, suggesting that ligation of 2B4 by CD48 on target cells was not necessary for 2B4 function. Rather, 2B4/CD48 interaction on adjacent T cells appeared to be critical for cytotoxicity. Therefore, 2B4 functions as a costimulator of CD8(+) T cells in MHC-restricted cytotoxicity. We conclude that 2B4/CD48 interactions among T cells themselves can augment CTL lysis of their specific targets.
Lee
Kyung-Mi
KM
Department of Pathology, University of Chicago, Chicago, IL 60637, USA. kyunglee@flowcity.bsd.uchicago.edu
Bhawan
Sadhna
S
Majima
Takashi
T
Wei
Hairong
H
Nishimura
Michael I
MI
Yagita
Hideo
H
Kumar
Vinay
V
D000276:Adjuvants, Immunologic / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D000071178:CD48 Antigen; D002450:Cell Communication / Q000235:genetics / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000502:physiology*; D005822:Genetic Vectors; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation / Q000235:genetics; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D012190:Retroviridae / Q000235:genetics; D000071176:Signaling Lymphocytic Activation Molecule Family; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D019138:Antibodies, Blocking; D015703:Antigens, CD; D000071178:CD48 Antigen; C490007:Cd244a protein, mouse; C000604066:Cd48 protein, mouse; D004268:DNA-Binding Proteins; D018984:Epitopes, T-Lymphocyte; D008024:Ligands; D008562:Membrane Glycoproteins; C499308:Rag2 protein, mouse; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family; C064655:V(D)J recombination activating protein 2