The mechanism of IL-2-mediated protection against GVHD in mice. II. Protection occurs independently of NK/LAK cells.
We have recently demonstrated that high-dose IL-2, when begun on the day of bone marrow transplantation, has a potent protective effect against graft-vs.-host disease mortality, especially when coadministered with T cell-depleted syngeneic bone marrow cells. Because several groups of investigators have demonstrated that lymphokine-activated killer cells can mediate GVHD protection, we hypothesized that the mechanism of protection by IL-2 administration might involve the in vivo activation of natural killer and/or LAK cells. In order to test this hypothesis, we evaluated the effect of IL-2 administration on the number of NK1+ cells and on NK-mediated cytotoxic activity in recipients of GVHD-producing inocula. Furthermore, we evaluated the effects on IL-2-induced GVHD protection of depleting NK cells and LAK precursor cells in vivo with mAb against NK1.1 or antiserum against asialo GM1. The results demonstrate that: (1) The number of NK1+ cells is not increased in spleens of IL-2-treated compared with control recipients of GVHD-producing inocula; (2) NK activity is not increased in IL-2-treated compared with control recipients of GVHD-producing inocula during or immediately following the period of IL-2 administration; (3) depletion of NK cells and LAK precursors from the donor and host influenced the time course of GVHD-related mortality in a complex fashion; and (4) IL-2-induced GVHD protection is largely independent of the activity of an NK or LAK cell population of donor or host origin. IL-2-induced GVHD protection therefore reflects primarily the activity of non-LAK protective cell populations, or it may be a direct inhibitory effect on responding donor cell populations as they encounter host antigen.
Sykes
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Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Charlestown 02129.
Abraham
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VS
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D005677:G(M1) Ganglioside / Q000276:immunology; D006086:Graft vs Host Disease / Q000517:prevention & control*; D007376:Interleukin-2 / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000502:physiology* / Q000648:ultrastructure; D007694:Killer Cells, Natural / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D007958:Leukocyte Count; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013997:Time Factors
D000906:Antibodies; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside