Evidence that monoclonal antibodies against the 55kD subunit of the rat IL-2 receptor do not inhibit the development of suppressor cells generated in mixed lymphocyte culture.
Although the ability of Ts to prevent allograft rejection has been well established, their intrinsic characteristics and dependence upon lymphokines remain poorly defined. The cells from unmodified LEWxBN bulk 5-day rat MLR inhibit both proliferation in test MLR and generation of CTL, as well as prolonging the survival of donor-specific test cardiac allografts following adoptive transfer. We have examined the effects of a panel of mAb directed against functionally distinct epitopes on the p55 subunit of rat IL-2R on the generation and in vitro/in vivo activity of MLR-generated Ts. ART-18 (which blocks IL-2-dependent T cell growth) was the only mAb from the panel that profoundly suppressed alloreactive T cell proliferation in primary MLR (47.5%). However, the generation of Ts was never affected by any mAb (% suppression in test MLR = 40-60%). Neither ART-18 nor ART-65 (which does not affect T cell proliferation) interfered with the efficacy of Ts to inhibit CTL generation in fresh bulk MLR. Adoptive transfer of cells (3-10 x 10(6] from ART-18 or ART-65-modulated MLR into naive LEW rats prolonged (LEW x BN)F1 test cardiac allograft survival to 11-13 days (P less than 0.05 as compared with acutely rejecting hosts). All in vitro and in vivo effects exerted by MLR-generated cells were antigen-specific. In unmodified MLR, Ts were IL-2R+ (ca. 50% of total blasts), as shown by cell separation using magnetic beads. In contrast, in MLR with ART-18 added, Ts were primarily IL-2R- (ca. 10% of blasts). Thus, antirat p55 subunit IL-2R mAb do not inhibit MLR-generated Ts functionally operative in vitro and in vivo. IL-2R- Ts precursors requiring lymphokine(s) other than IL-2 may differentiate into IL-2-dependent Ts effectors. Such divergent IL-2 requirements for Ts growth in vitro may explain the Ts-sparing effects in allograft recipients treated with anti-IL-2R mAb.
Tanaka
K
K
Surgical Research Laboratory, Harvard Medical School, Boston, MA.
Turka
L A
LA
Kupiec-Weglinski
J W
JW
Milford
E L
EL
Ueda
H
H
Diamantstein
T
T
Carpenter
C B
CB
Tilney
N L
NL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D005434:Flow Cytometry; D007376:Interleukin-2 / Q000502:physiology; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D015375:Receptors, Interleukin-2