Minor antigens on transfused RBCs crossprime CD8 T cells but do not induce full effector function

Area of Science:

• Immunology
• Transplantation immunology

Background:

• HLA-matched bone marrow transplantation (BMT) is curative for hematological disorders.
• High rejection rates after BMT correlate with prior transfusions, suggesting an immunogenic component in transfused products.
• Previous studies implicated minor antigens (mHAs) on transfused cells in BMT rejection.

Purpose of the Study:

• To investigate the role of red blood cells (RBCs) as an immunogen in inducing BMT rejection.
• To determine if RBC-expressed mHAs alone can sensitize recipients to subsequent BMT.

Main Methods:

• Utilized transgenic HOD mice expressing a model mHA exclusively on RBCs.
• Transfused HOD blood into recipients and assessed BMT rejection.
• Evaluated endogenous anti-HOD CD8(+) T-cell responses using tetramer reagents.
• Adoptively transferred OT-I T cells to assess their expansion, phenotype, and cytotoxic activity post-transfusion.

Main Results:

• Transfusion of HOD blood did not induce BMT rejection in recipients sharing mHAs with HOD RBCs.
• No endogenous anti-HOD CD8(+) T-cell response was detected.
• Adoptively transferred OT-I T cells showed transient expansion and a semi-effector phenotype (TNF-α, IFN-γ secretion, minimal Granzyme B).
• In vivo cytotoxic T-lymphocyte (CTL) assays revealed only transient lytic activity.

Conclusions:

• RBCs expressing mHAs may not be the primary driver of BMT rejection.
• The immunogenic component in RBC units responsible for BMT rejection might be contaminating platelets or leukocytes.