Indirect T-cell allorecognition and the mechanisms of immunosuppression by allogeneic blood transfusions

Abstract

LEW rats given twice weekly intravenous transfusions of DA blood for 10 weeks showed a strong antibody response to intact DA class I antigens at day 7 that declined to undetectable levels by week 6. The response remained undetectable for the remainder of the course, in spite of the repeated transfusions of DA blood. At week 6 during the blood transfusion course, the LEW rats were immunised with a DA class I peptide known to be recognised by LEW CD4 + T cells in a LEW APC-dependent manner. This resulted in the prompt reappearance of a strong antibody response to intact DA class I antigen. However, in vitro T-cell proliferation responses to peptide 1 appeared to be partially suppressed by the blood transfusions. Immunisation of LEW rats with this peptide 4 weeks before commencement of the course of DA blood transfusions prevented the decline in antibody levels normally seen during the blood transfusion course. These data indicate that the multiple blood transfusions are able to induce, in non-sensitised recipients, a reversible suppression of the indirect T-helper response specific for allogeneic peptides in the blood transfusion. Although our protocol of twice weekly transfusions does not correspond to the clinical pattern of blood transfusions, our results raise the possibility that antigenic cross-reactivity at the level of small polymorphic MHC peptides between blood and organ donors might represent the immunological basis for the beneficial effects of random blood transfusions.