Blood Transfusion and Immunomodulation : A Possible Mechanism

Abstract

To induce an immunogenic response in vivo, an antigen-presenting (stimulator) cell must present both antigen-specific (class II MHC) and an accessory signal to the CD4 T cell. Failure to express the accessory signal has been shown in vitro to induce a state of specific unresponsiveness (anergy) in the T cell. We have shown that although stimulator cells in blood continue to express class II MHC molecules during refrigerated storage, their ability to present the accessory signal diminishes, reaching zero in all units tested by about 13 days. This implies that blood in excess of 2 weeks old should not alloimmunize but could induce some degree of immunosuppression. UV-B irradiation and, to a lesser extent, gamma-irradiation, were also shown to inhibit expression of the accessory signal by stimulator cells in blood.

Deleterious clinical effects of transfusion-associated immunomodulation: fact or fiction?

“…Therefore, it would be logical to implement measures to prevent these immunomodulatory effects of allogeneic blood transfusion. Because most evidence from studies in experimental animals implicates allogeneic WBCs in the production of the deleterious TRIM effects, 30,[37][38][39][40][41][42][43] and because universal WBC reduction of all transfused cellular blood components has been implemented in some western European countries and in Canada, 50,51 policy makers in the United States and elsewhere are currently considering the question of implementing universal WBC reduction for the purpose of preventing the various possible deleterious TRIM effects.…”

“…11,26,27 The mechanism(s) of the TRIM effect(s) also remains elusive, and it is possible that a large number of biologic mechanisms may underlie the effect(s). [28][29][30][31] The infusion of foreign antigen in either a soluble [31][32][33][34][35][36] or cell-associated [37][38][39][40][41][42][43] form has been shown to induce immune suppression, anergy, and clonal deletion in studies in experimental animals. However, most studies evaluating proposed mechanisms have been done in rodents, and these findings may not be applicable to the human immune system.…”

“…Allogeneic plasma, [31][32][33][34][35][36] allogeneic WBCs, 30,[37][38][39][40][41][42][43] and substances that accumulate in blood components during storage 39 have been implicated in the pathogenesis of TRIM. However, both the animal and human data suggest that the TRIM effects are most likely mediated by transfused allogeneic WBCs.…”

“…These and several other investigators 41,42 also attributed an induction of T H 2 cells in transfusion recipients to the allogeneic donor WBCs, showing that T H 2 cells can produce immunosuppression in transfusion recipients by down-regulating the activity of T H 1 cells. Mincheff et al 43 implicated the antigen-presenting cells of the allogeneic donor in the induction of a state of anergy in the recipient and proposed that, during refrigeration, antigen-presenting cells lose their ability to deliver costimulation. These investigators hypothesized that after an allogeneic transfusion, the recipient's T cells are stimulated by allogeneic donor WBCs in the absence of costimulation and that this interaction induces a state of anergy in the recipient's T cells.…”

Stored blood - an effective immunosuppressive method for transplantation of kidneys from unrelated donors: An 11-year follow-up

“…Mincheff et al (24) have shown that blood stored for 13 or more days loses its immunogenicity because its ability to present the accessory signal diminishes, with a Creatinine (mg/dl)(-¢-) consequent induction of some degree of immunosuppression.…”