Conventional liver CD4 T cells are functionally distinct and suppressed by environmental factors.
The contribution of intrahepatic conventional T cells to the unique immunologic properties of the liver has not been clearly defined. We isolated bulk and CD4 T cells from mouse liver and compared their functions with each other and with their splenic counterparts. Unlike bulk spleen T cells, bulk liver T cells reacted minimally to allogeneic or antigen-loaded syngeneic dendritic cells. However, after exclusion of natural killer T cells (NKTs) and gammadelta T cells by FACS, liver and spleen CD4 T cells actually proliferated to a similar extent upon allogeneic or antigen-specific stimulation. Liver CD4 T cells were more sensitive to interleukin 2 (IL-2) than were spleen CD4 T cells, but had a similar proliferative potential based on their response to CD3 ligation. In addition, activated liver CD4 T cells produced higher levels of IL-4, IL-5, IL-10, and interferon gamma (IFN-gamma) than did splenic CD4 T cells. Therefore, liver CD4 T cells are intrinsically different from spleen CD4 T cells. In vitro, liver or spleen NKTs and gammadelta T cells suppressed liver and spleen CD4 T-cell proliferation in a dose-dependent fashion. In conclusion, unconventional T cells constrain liver CD4 T-cell function. Our findings have implications for pathological conditions of the liver that involve the response of conventional CD4 T lymphocytes.
Katz
Steven C
SC
Hepatobiliary Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Pillarisetty
Venu G
VG
Bleier
Joshua I
JI
Kingham
T Peter
TP
Chaudhry
Umer I
UI
Shah
Alaap B
AB
DeMatteo
Ronald P
RP
D000818:Animals; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000502:physiology; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000494:pharmacology; D008099:Liver / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000502:physiology; D013154:Spleen / Q000276:immunology
D016207:Cytokines; D007376:Interleukin-2; D016692:Receptors, Antigen, T-Cell, gamma-delta