The effect of a novel immunosuppressant, FTY720, in mice without secondary lymphoid organs.
OBJECTIVE
FTY720 is a novel immunosuppressive agent that is thought to reduce the number of peripheral blood lymphocytes (PBL) by directing them toward secondary lymphoid organs such as the lymph nodes and Peyer's patches. We studied the effects of FTY720 on aly/aly mice that do not have either lymph nodes or Peyer's patches, as well as on splenectomized aly/aly mice.


METHODS
FTY720 was orally administered by gavage (1 mg/kg) to aly/aly mice as well as to aly/+ mice with and without a splenectomy on 14 consecutive days. The number of lymphocytes was then counted using True Cell beads and flow cytometry. The number of B220-, CD3-, and CD4-positive cells was also determined. In addition, skin grafts from C3H donor mice were performed on these mice.


RESULTS
FTY720 was effective in significantly reducing the total lymphocyte count as well as the B220-, CD3-, and CD4-positive subtypes in the peripheral blood of aly/+ mice as well as in aly/aly mice with and without a splenectomy. While we did observe allograft skin graft rejection in both the aly/+ mice as well as the aly/aly mice recipients and splenectomized aly/aly mice, the graft survival was prolonged in all groups. The skin allografts treated by FTY720 thus demonstrated fewer lymphocytic cells and less infiltration of CD4-positive cells.


CONCLUSIONS
The administration of FTY720 to mice without lymph nodes, Peyer's patches, or spleens still results in peripheral lymphopenia. In all groups, FTY720 was found to prevent the infiltration of CD4-positive cells in skin allografts while also prolonging skin allograft survival. The fate of these lymphocytes, however, is unclear.
Sugito
Kiminobu
K
Division of Pediatric Surgery, Department of Surgery, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan.
Koshinaga
Tsugumichi
T
Inoue
Mikiya
M
Ikeda
Taro
T
Hagiwara
Noritsugu
N
Fukuzawa
Masahiro
M
D000818:Animals; D000068876:Fingolimod Hydrochloride; D006085:Graft Survival; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology*; D008206:Lymphatic Diseases; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000187:drug effects*; D008221:Lymphoid Tissue / Q000187:drug effects*; D008231:Lymphopenia / Q000139:chemically induced / Q000209:etiology*; D008297:Male; D051379:Mice; D011409:Propylene Glycols / Q000009:adverse effects / Q000494:pharmacology*; D016038:Skin Transplantation / Q000276:immunology; D013110:Sphingosine / Q000031:analogs & derivatives; D013156:Splenectomy; D018344:T-Lymphocytopenia, Idiopathic CD4-Positive / Q000139:chemically induced / Q000209:etiology
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine