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Non-Host-Reactive Donor CD8+ T Cells of Tc2 Phenotype
Potently Inhibit Marrow Graft Rejection
Daniel H. Fowler,
Bernard Whitfield,
Michael Livingston,
Paul Chrobak, and
Ronald E. Gress
From the Transplantation Therapy Section, Medical Oncology Branch and
Experimental Immunology Branch, National Cancer Institute, National
Institutes of Health, Bethesda, MD.
Donor CD8+ T cells capable of host reactivity inhibit
marrow graft rejection, but also generate graft-versus-host disease
(GVHD). To evaluate whether the Tc1- and Tc2-type subsets of CD8 cells might inhibit rejection without host reactivity, we established an F1
into-parent murine bone marrow transplant model. Donor Tc1 and Tc2
cells were generated that preferentially secreted type I or type II
cytokines; both subsets possessed potent cytolytic function, and
clonally deleted host-type allospecific precursor CTL in
vitro. B6 hosts receiving 950 cGy irradiation did not reject the donor
marrow (F1 chimerism of 78.6%; n = 10), whereas hosts receiving 650 cGy rejected the donor marrow (3.8% chimerism; n = 8). At 650 cGy
irradiation, the addition of Tc2 cells to the F1 marrow resulted in
extensive F1 chimerism (70.8%) in 8 of 8 recipients; in contrast,
alloengraftment was not consistently observed in mice receiving Tc1
cells or unmanipulated CD8 cells. Furthermore, when the preparative
regimen was further reduced to 600 cGy, only hosts receiving the
Tc2-type cells did not reject the F1 marrow. We conclude that Tc2 cells
potently inhibit marrow graft rejection without inducing an
alloaggressive response and that non-host-reactive Tc2 cells therefore
facilitate engraftment across genetic barriers with reduced GVHD.
Blood, Vol. 91 No. 11 (June 1), 1998:
pp. 4045-4050
© 1998 by The American Society of Hematology.
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