Induction and suppression of delayed-type hypersensitivity to non-MHC antigens during lethal graft-versus-host reaction.
A delayed-type hypersensitivity reaction (DTH) to non-MHC Ag was detected during a lethal graft-vs-host reaction (GVH) induced by incompatibility for non-MHC Ag alone. In this model, when appropriate doses of B10.D2 bone marrow and lymphoid cells are grafted to irradiated (DBA/2 x B10.D2)F1 recipients, the ensuing GVH, directed against those DBA/2 non-MHC Ag absent from the B10.D2 background, results in virtually 100% mortality in less than 3 mo; donor alloimmunization against the host histocompatibility Ag considerably reduces mortality, and survival rates of 80 to 100% are common. The experiments reported here show that: 1) the cell responsible for DTH induction expresses the CD4+ CD8- phenotype; 2) CD4+ cells likewise seem to play a predominant role in the pathology of lethal GVH in this genetic combination; 3) the alloimmunization protocol that abrogates mortality also abolishes GVH-associated DTH; and 4) this suppressive effect, as shown elsewhere for the protection against mortality, is mediated by CD4- CD8- "double negative" Thy-1+ CD3+ T suppressor cells. Thus, there is a good parallel between lethal GVH and its associated DTH as concerns both induction and suppression of the two phenomena, suggesting that mortality and DTH may represent different manifestations of a common underlying mechanism. Initiation of the effector phase of DTH in the adoptive transfer model seems to be dependent on the presence of a Thy-1+ double-negative cell in the transfer inoculum; the possible relationship of this double-negative cell to the Th-1-type CD4+ DTH-mediating cell recently shown to induce lethal GVH is discussed.
Pritchard
L L
LL
INSERM U.267, Groupe Hospitalier Paul Brousse, Villejuif, France.
Huchet
R
R
Bruley-Rosset
M
M
Riché
N
N
Mishal
Z
Z
Halle-Pannenko
O
O
D000818:Animals; D000941:Antigens / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis; D006087:Graft vs Host Reaction / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007111:Immunity, Cellular; D007114:Immunization; D008212:Lymphocyte Depletion; D051379:Mice; D008815:Mice, Inbred Strains; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000941:Antigens; D016827:CD8 Antigens