The CD4⁺ T-cell help signal is transmitted from APC to CD8⁺ T-cells via CD27-CD70 interactions.
CD8(+) cytotoxic T lymphocytes are critical components of immunity against infectious pathogens, tumours, and in the case of pathogenic autoimmunity, normal self tissues. CD4(+) T (T(H)) cells provide 'help' to CD8(+) cytotoxic T lymphocytes during priming by first activating antigen-presenting cells via CD40-CD40L interactions. Here we show that, after immunization with either a noninflammatory, nonreplicating antigen or an overtly inflammatory replicating antigen, CD8(+) cytotoxic T lymphocytes prevented from receiving a signal through CD27 during priming subsequently exhibit a specific defect in their capacity for secondary expansion that can be rescued by the absence of TRAIL. Thus, the 'help message' is transmitted to CD8(+) T cells via CD70-CD27 signals, enabling them to undergo secondary expansion and avoid TRAIL-mediated apoptosis on re-stimulation. These findings complete our understanding of the cellular interactions through which T(H) is provided to CD8(+) cytotoxic T lymphocytes during priming.
Laboratory of Cellular Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, California                 92037, USA.
Sonia
S
Feau
Zacarias
Z
Garcia
Ramon
R
Arens
Hideo
H
Yagita
Jannie
J
Borst
Stephen P
SP
Schoenberger
D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism*; D053282:CD27 Ligand / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002478:Cells, Cultured; D005434:Flow Cytometry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011485:Protein Binding; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000235:genetics / Q000378:metabolism*
D053282:CD27 Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D023201:CD40 Ligand