IL-7 drives donor T cell proliferation and can costimulate cytokine secretion after MHC-matched allogeneic bone marrow transplantation.
Transplantation of MHC-matched, allogeneic B10.D2 bone marrow plus T cells into BALB/c recipients ultimately results in chronic graft-vs-host disease (GVHD) and mortality 8 to 12 wk post-transplant. We have identified IL-7-specific mRNA in the spleens of BALB/c bone marrow transplantation (BMT) recipients during the first week post-transplant. The response by T cells from B10.D2-->BALB/c BMT recipients to stimulation with IL-7 in vitro during the early period after transplant was then examined. The findings indicated that within the first week post-transplant, spleen cells removed from recipients injected with allogeneic, but not syngeneic, T cells proliferated vigorously to rIL-7. Both IL-2-dependent and -independent components were identified. Depletion of responding cells before culture with anti-Thy-1.2 Ab virtually eliminated this response. We conclude that transplant of allogeneic T cells is required for the observed IL-7 response, and moreover, such cells proliferate after exposure to this cytokine in vitro. To determine whether IL-7 could have a functional effect on donor T cells, the production of IFN-gamma by T cells from allogeneic BMT recipients stimulated with anti-T cell receptor (i.e., anti-V beta) Ab was examined. IL-7 was demonstrated to enhance IFN-gamma production by donor T cells postallogeneic BMT. These results suggest that a cytokine presumably produced in the host for the physiologic function of hematologic reconstitution is playing an additional role during the early events after allogeneic BMT mediated via the expansion and augmented cytokine production by donor T cells.
Levy
R B
RB
Department of Microbiology and Immunology, University of Miami School of Medicine, FL 33101.
Jones
M
M
Hamilton
B L
BL
Paupe
J
J
Horowitz
T
T
Riley
R
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001483:Base Sequence; D016026:Bone Marrow Transplantation / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D015851:Interleukin-7 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology*; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011828:Radiation Chimera; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation
D000911:Antibodies, Monoclonal; D016207:Cytokines; D015851:Interleukin-7; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma