Specific elimination of alloreactive T cells by an anti-interleukin-2 receptor B chain-specific immunotoxin.
Graft-versus-host disease and graft rejection remain the two principal causes of morbidity and mortality after major-histocompatibility-complex-mismatched bone marrow transplantation. Human and animal models suggest that both CD4+ and CD8+ T cell subsets present in the donor inoculum are responsible for their initiation. Since the human mixed lymphocyte culture (MLC) and the HLA-restricted cytotoxicity may reflect cellular interactions occurring during GVHD and graft rejection, inhibitions of these responses may represent useful approaches for screening functional T cell depletion in experimental bone marrow transplantation studies. For this purpose, we have tested the possibility of removing the host-specific allogeneic T cells present in the marrow. After a two-day MLC, the specifically activated host alloreactive blood or bone marrow T cells were incubated with the ricin A-chain toxin conjugated with the antibody 33B3.1 directed against the human receptor of interleukin 2 (33B3.1-IT). A complete inhibition of a primary MLC and of cytotoxic activities was observed as well as a disappearance of IL-2R(+) (p55) T cells. This method had limited consequence upon the alloreactivity of blood or marrow T cells toward a third unrelated party. The limiting-dilution analysis of residual alloantigen-reactive T lymphocytes has shown that this depletion results in a twentyfold to fiftyfold reduction of antihost reactivity. The procedure was also shown not to inhibit the growth of marrow precursors for granulocytes and macrophages.
Cavazzana-Calvo
M
M
Centre de Transfusion Sanguine, Hôpital Necker, Paris, France.
Fromont
C
C
Le Deist
F
F
Lusardi
M
M
Coulombel
L
L
Derocq
J M
JM
Gerota
I
I
Griscelli
C
C
Fischer
A
A
D006412:Hematopoietic Stem Cells; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology*; D007519:Isoantigens / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008212:Lymphocyte Depletion; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D012276:Ricin / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology*
D000922:Immunotoxins; D007519:Isoantigens; D015375:Receptors, Interleukin-2; D012276:Ricin