Intrahepatic CD8(+) lymphocyte trapping during tolerance induction using mushroom derived formulations: a possible role for liver in tolerance induction.
OBJECTIVE
To determine the immunomodulatory effect of Shiitake (a mushroom extract), we tested its effect on liver-mediated immune regulation in a model of immune-mediated colitis.


METHODS
Four groups of mice were studied. Colitis was induced by intracolonic instillation of TNBS in groups A and B. Groups A and C were treated daily with Shiitake extract, while groups B and D received bovine serum albumin. Mice were evaluated for development of macroscopic and microscopic. The immune effects of Shiitake were determined by FACS analysis of intra-hepatic and intrasplenic lymphocytes and IFN-gamma ELISPOT assay.


RESULTS
Administration of Shiitake resulted in marked alleviation of colitis, manifested by significant improvement in the macroscopic and microscopic scores, and by reduction in IFN-gamma-producing colonies in group A, compared to group B mice (1.5 pfu/mL vs 3.7 pfu/mL, respectively). This beneficial effect was associated with a significant increase in the intra-hepatic CD8(+) lymphocyte trapping, demonstrated by an increased intrasplenic/intrahepatic CD4/CD8 lymphocyte ratio. These effects were accompanied by a 17% increase in the number of intrahepatic natural killer T (NKT) cells. A similar effect was observed when Shiitake was administered to animals without disease induction.


CONCLUSIONS
Shiitake extract affected liver-mediated immune regulation by altering the NKT lymphocyte distribution and increasing intrahepatic CD8(+) T lymphocyte trapping, thereby leading to alleviation of immune-mediated colitis.
Shuvy
Mony
M
Liver Unit, Department of Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
Hershcovici
Tiberiu
T
Lull-Noguera
Cristina
C
Wichers
Harry
H
Danay
Ofer
O
Levanon
Dan
D
Zolotarov
Lidya
L
Ilan
Yaron
Y
D000818:Animals; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology*; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D007108:Immune Tolerance / Q000187:drug effects*; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010936:Plant Extracts / Q000494:pharmacology*; D012720:Severity of Illness Index; D020942:Shiitake Mushrooms; D014302:Trinitrobenzenesulfonic Acid
D010936:Plant Extracts; D007371:Interferon-gamma; D014302:Trinitrobenzenesulfonic Acid