Active suppression of host-vs graft reaction in pregnant mice. IX. Soluble suppressor activity obtained from allopregnant mouse decidua that blocks the cytolytic effector response to IL-2 is related to transforming growth factor-beta.
Non-Ts cells in murine allopregnancy decidua release potent immunosuppressor factors in vitro that block the action of IL-2. Previous studies have shown that both primary and secondary CTL responses are inhibited as well as the generation of Il-2 activated killer cells. In this paper we show that the suppressor factor(s) can arrest ongoing IL-2 dependent CTL responses but does not block binding of anti-IL-2R antibody or radiolabeled IL-2 to the IL-2R. The suppressive activity is associated with molecules that adhere to hydroxylapatite and con A-agarose but do not bind to activated charcoal or partition as lipids. HPLC TSK 3000 separation showed a major peak of suppressive activity at 60 to 100 kDa, with additional activity at 300 kDa, and at less than 1000. Under acid conditions, suppressive activity resolved as a major peak at 13 kDa with some residual activity at 65 kDa and at less than or equal to 1000. A specific rabbit IgG antibody to transforming growth factor-beta neutralized suppressor activity in unseparated supernatant and in the 13-kDa fraction whereas neutralizing antibodies to progesterone or PGE-2 did not affect suppression but could neutralize their respective ligands. Inasmuch as transforming growth factor-beta has a 25 kDa Mr, the 13-kDa decidua-associated suppressor factor would appear to represent a related but distinct regulatory molecule that associates with a variety of carrier molecules.
Clark
D A
DA
McMaster University, Hamilton, Ontario, Canada.
Falbo
M
M
Rowley
R B
RB
Banwatt
D
D
Stedronska-Clark
J
J
D000818:Animals; D001667:Binding, Competitive; D003602:Cytotoxicity, Immunologic; D003656:Decidua / Q000276:immunology*; D005260:Female; D006087:Graft vs Host Reaction; D007112:Immunity, Maternally-Acquired; D007376:Interleukin-2; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D008970:Molecular Weight; D011247:Pregnancy; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013491:Suppressor Factors, Immunologic / Q000302:isolation & purification / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D015291:Transforming Growth Factors / Q000276:immunology
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D013491:Suppressor Factors, Immunologic; D015291:Transforming Growth Factors