CD8+CD44(hi) but not CD4+CD44(hi) memory T cells mediate potent graft antilymphoma activity without GVHD.
Allogeneic hematopoietic cell transplantation can be curative in patients with leukemia and lymphoma. However, progressive growth of malignant cells, relapse after transplantation, and graft-versus-host disease (GVHD) remain important problems. The goal of the current murine study was to select a freshly isolated donor T-cell subset for infusion that separates antilymphoma activity from GVHD, and to determine whether the selected subset could effectively prevent or treat progressive growth of a naturally occurring B-cell lymphoma (BCL(1)) without GVHD after recipients were given T cell-depleted bone marrow transplantations from major histocompatibility complex-mismatched donors. Lethal GVHD was observed when total T cells, naive CD4(+) T cells, or naive CD8(+) T cells were used. Memory CD4(+)CD44(hi) and CD8(+)CD44(hi) T cells containing both central and effector memory cells did not induce lethal GVHD, but only memory CD8(+) T cells had potent antilymphoma activity and promoted complete chimerism. Infusion of CD8(+) memory T cells after transplantation was able to eradicate the BCL(1) lymphoma even after progressive growth without inducing severe GVHD. In conclusion, the memory CD8(+) T-cell subset separated graft antilymphoma activity from GVHD more effectively than naive T cells, memory CD4(+) T cells, or memory total T cells.
Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Suparna
S
Dutt
Jeanette
J
Baker
Holbrook E
HE
Kohrt
Neeraja
N
Kambham
Mrinmoy
M
Sanyal
Robert S
RS
Negrin
Samuel
S
Strober
D000818:Animals; D001835:Body Weight; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002455:Cell Division; D045744:Cell Line, Tumor; D018450:Disease Progression; D006086:Graft vs Host Disease / Q000150:complications / Q000276:immunology*; D018960:Hyaluronan Receptors / Q000378:metabolism*; D007114:Immunization; D007156:Immunologic Memory / Q000276:immunology*; D008223:Lymphoma / Q000150:complications / Q000276:immunology* / Q000628:therapy; D051379:Mice; D009928:Organ Specificity / Q000276:immunology; D010641:Phenotype; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016019:Survival Analysis; D016176:T-Lymphocyte Subsets / Q000637:transplantation
D018960:Hyaluronan Receptors
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