Suppression by alpha-fetoprotein of murine natural killer cell activity stimulated in vitro and in vivo by interferon and interleukin 2.
Natural killer (NK) cells are 'spontaneously' cytotoxic cells thought to be involved in surveillance against tumour cells, rejection of virally infected cells, and regulation of haematopoietic stem cell differentiation and antibody synthesis. Fetus-derived alpha-fetoprotein (AFP) has been shown to regulate certain T cell-mediated immune reactions in vitro and in vivo. The lack of NK activity in newborn mice with high endogenous levels of AFP, together with the presence of cells expressing NK surface markers, also suggests that AFP may regulate NK activity. In this study we compared the effects of AFP on spontaneous versus activated murine NK activity. The lytic ability of both freshly prepared splenic NK cells and those arising after incubation for 24 h with interferon, Poly I:C, or T-cell growth factor (TCGF) was not affected by AFP if the latter was present only during the killing phase. However, if AFP was added at the beginning and retained for the duration of the 24-h in vitro lymphokine stimulation, the subsequent NK activity induced by interferon, Poly I:C, and TCGF was found to be significantly suppressed. This inhibition is both dose- and time-dependent. Delayed addition experiments showed that when AFP is present during the first 6 h of in vitro stimulation it will suppress interferon and TCGF-boosted NK activity by 50-80%. The AFP-mediated inhibitory effect on lymphokine-stimulated NK activity is not the result of increased death of effector cells nor, in the case of interferon and polyribonucleotides, of non-specific binding of AFP to the enhancing agents. In vivo injections of Poly I:C or TCGF failed to increase neonatal NK function, while administration of interferon did cause slightly higher levels of NK activity. However, spleen cells from newborn animals cultured for 24 h in the presence of lymphokines resulted in markedly elevated NK function and this in vitro activation could be suppressed by purified fetus-derived AFP. Thus, the in vivo pattern of NK activation in newborns with high endogenous levels of AFP was very similar to that of adult NK stimulation in vitro when exogenous AFP was added.
B L
BL
Cohen
A
A
Orn
K O
KO
Gronvik
M
M
Gidlund
H
H
Wigzell
R A
RA
Murgita
D000818:Animals; D000831:Animals, Newborn; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007372:Interferons / Q000378:metabolism / Q000494:pharmacology*; D007376:Interleukin-2 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D011070:Poly I-C / Q000494:pharmacology; D000509:alpha-Fetoproteins / Q000378:metabolism / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D007376:Interleukin-2; D000509:alpha-Fetoproteins; D007372:Interferons; D011070:Poly I-C