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.