Interleukin-10 but not transforming growth factor-beta is essential for generation and suppressor function of regulatory cells induced by intratracheal delivery of alloantigen.
BACKGROUND
We previously reported that intratracheal delivery of alloantigen-induced regulatory cells in mouse heart-transplantation model. Here, we investigated roles of interleukin (IL)-10 and transforming growth factor (TGF)-beta in induction and effector phases of the regulatory cells.


METHODS
CBA mice were pretreated with intratracheal delivery of C57BL/10 splenocytes and administration of neutralizing anti-IL-10 or anti-TGF-beta monoclonal antibody (mAb). Seven days after the pretreatment, naive CBA mice (secondary recipients) were given adoptive transfer of splenocytes from the pretreated mice and underwent heart grafting from C57BL/10 mice. To determine roles of these cytokines in the effector phase of the regulatory cells, anti-IL-10 or anti-TGF-beta mAb was administered weekly into the secondary recipients after the adoptive transfer.


RESULTS
Adoptive transfer of splenocytes from CBA mice that had been pretreated with intratracheal delivery of C57BL/10 splenocytes significantly prolonged the survival of C57BL/10 allograft (median survival time [MST] 68 days) as compared with adoptive transfer from untreated CBA mice (MST 12 days). In the induction phase, anti-IL-10 mAb abrogated development of the regulatory cells that afforded prolonged allograft survival in the secondary recipients (MST 20 days), whereas anti-TGF-beta mAb did not abrogate it (MST 88 days). In the effector phase, anti-IL-10 mAb abrogated prolonged allograft survival afforded by adoptive transfer of the regulatory cells in the secondary recipients (MST 27 days), whereas anti-TGF-beta mAb did not abrogate suppressor function of the regulatory cells (MST 53 days).


CONCLUSIONS
IL-10 but not TGF-beta was required for generation and suppressor function of the regulatory cells induced by intratracheal delivery of alloantigen.
Aramaki
Osamu
O
Department of Surgery, Teikyo University, Tokyo, Japan.
Inoue
Fumihiko
F
Takayama
Tadatoshi
T
Shimazu
Motohide
M
Kitajima
Masaki
M
Ikeda
Yoshifumi
Y
Okumura
Ko
K
Yagita
Hideo
H
Shirasugi
Nozomu
N
Niimi
Masanori
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D006084:Graft Rejection; D016753:Interleukin-10 / Q000502:physiology*; D007519:Isoantigens / Q000008:administration & dosage / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014019:Tissue Donors; D014132:Trachea; D016212:Transforming Growth Factor beta / Q000502:physiology*
D000911:Antibodies, Monoclonal; D007519:Isoantigens; D016212:Transforming Growth Factor beta; D016753:Interleukin-10