Submitted December 9, 2008
Accepted March 22, 2009
Regulatory T cell status in red cell alloimmunized responder and non-responder mice
Weili Bao, Jin Yu, Susanne Heck, and Karina Yazdanbakhsh*
Laboratory of Complement Biology, New York Blood Center, New York, NY, United States
Department of Integrative Medicine and Neurobiology, Shanghai Medical College, Fudan University, Shanghai, China
Flow Cytometry Laboratory, New York Blood Center, New York, NY, United States
* Corresponding author; email: kyazdanbakhsh{at}nybloodcenter.org.
Red blood cell (RBC) alloimmunization remains a major complication for transfusion-dependent patients, but immune factors governing risk for alloimmunization are unknown. We hypothesized that CD4+ regulatory T cell (Tregs) which we have shown control the rate and the frequency of RBC alloimmunization in mouse models may dictate responder/non-responder status. Using a transfusion regimen in which over 50% of mice develop alloantibodies to human glycophorin A antigen, we found reduced in vitro and in vivo Treg suppressive activity in responders compared to non-responders that was due to impaired Treg suppressor function. Moreover, responders were prone to developing additional alloantibodies to strong immunogens, while non-responders were resistant to alloimmunization. Altogether, our data raise the possibility that Treg activity may be used as a marker for identifying responder/non-responder status in transfusion recipients.
