Augmentation of post transplant immunity: antigen encounter at the time of hematopoietic stem cell transplantation enhances antigen-specific donor T-cell responses in the post transplant repertoire.
After transplant, the immune system is reconstituted by cells derived from both hematopoietic stem cells and peripheral expansion from differentiated donor T cells. After transplant, immune function is poor despite transplantation of mature lymphocytes from immune-competent donors. We tested the hypothesis that early antigen encounter at the time of cell transplant would improve the desired donor T-cell responses. Two independent models of peptide-specific T-cell responses were studied. The model for CD4 cells employed T cells from transgenic (Tg) DO11.11 mice that constitutively express the T-cell receptor for the class II-restricted ovalbumin peptide 323-339. The model for CD8 cells employed non-Tg H2-Db-restricted T-cell responses to the influenza nucleoprotein peptide 366-374. As measured both functionally and by direct imaging of T cells using clonotypic reagents, encounter with specific antigen at the time of T-cell transplantation led to clonal expansion of donor T cells and preservation of donor T-cell function in the post transplant immune environment. Antigen-specific donor T-cell function was poor if antigen encounter was delayed or omitted. Severe parent>F1 graft-versus-host reactions blocked the effect of early antigen exposure. Vaccination of transplant recipients against microbial or leukemia antigens may be worthy of study.
Mori
S
S
Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Kocak
U
U
Shaw
J L
JL
Mullen
C A
CA
D000818:Animals; D000941:Antigens / Q000737:chemistry / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000379:methods*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005452:Fluoresceins / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000494:pharmacology; D006086:Graft vs Host Disease / Q000276:immunology; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010455:Peptides / Q000737:chemistry; D013154:Spleen / Q000166:cytology; D013388:Succinimides / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D000941:Antigens; D005452:Fluoresceins; D005456:Fluorescent Dyes; D010455:Peptides; D013388:Succinimides