CRTAM confers late-stage activation of CD8+ T cells to regulate retention within lymph node.
In vivo immune response is triggered in the lymph node, where lymphocytes for entry into, retention at, and migration to effector sites are dynamically regulated. The molecular mechanism underlying retention regulation is the key to elucidating in vivo regulation of immune response. In this study, we describe the function of the adhesion molecule class I-restricted T cell-associated molecule (CRTAM) in regulating CD8+ T cell retention within the lymph node and eventually effector function. We previously identified CRTAM as a receptor predominantly expressed on activated CD8+ T cells, and nectin-like molecule-2 (Necl2) as its ligand. In vivo function of CRTAM-Necl2 interaction was analyzed by generating CRTAM(-/-) mice. CRTAM(-/-) mice exhibited reduced protective immunity against viral infection and impaired autoimmune diabetes induction in vivo. Although Ag-specific CRTAM(-/-) CD8+ T cells showed normal CTL functions in vitro, their number in the draining lymph node was reduced. Because CRTAM+ T cells bound efficiently to Necl2-expressing CD8+ dendritic cells (DCs) that reside in T cell area of lymph node, CRTAM may induce retention by binding to CD8+ DCs at the late stage of activation before proliferation. The CRTAM-mediated late interaction with DCs induced retention of activated CD8+ T cells in an Ag-independent fashion, and this possibly resulted in effective CTL development in the draining lymph node.
Takeuchi
Arata
A
Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan.
Itoh
Yasushi
Y
Takumi
Akiko
A
Ishihara
Chitose
C
Arase
Noriko
N
Yokosuka
Tadashi
T
Koseki
Haruhiko
H
Yamasaki
Sho
S
Takai
Yoshimi
Y
Miyoshi
Jun
J
Ogasawara
Kazumasa
K
Saito
Takashi
T
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000473:pathology; D002464:Cell Migration Inhibition / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007136:Immunoglobulins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013997:Time Factors
D018984:Epitopes, T-Lymphocyte; D007136:Immunoglobulins; C408522:class-I restricted T cell-associated molecule