Mixed lymphocyte reaction
Mixed lymphocyte reaction is a test used by pharmaceutical and biotech organizations to show the safety of a drug or implantable material. It is commonly used as part of the FDA clearance process. Put simply, it is mixing populations of T-lymphocytes together, and measuring the reaction that occurs. Technically, it is an ex-vivo cellular immune assay that occurs between two allogeneic lymphocyte populations. In a one-way MLR, only one lymphocyte population can respond or proliferate. In a two-way MLR, both populations can proliferate. MLR’s are performed to assess how T-cells react to external stimuli. T cells are a type of white blood cell that scans for cellular abnormalities and infections. They are essential to human immunity.
History & background
The MLR was first recognized when researchers mixed leukocytes from two unrelated donors in culture. After several days, lymphocytes underwent blast transformation, DNA synthesis and cellular proliferation in response to the major histocompatibility antigen differences between the two cell populations designated as Responder and Stimulator cells. Responder cells proliferated without previous exposure to Stimulator MHC antigens. This response became quantifiable when incorporating radioactive labelled thymidine or 5-bromo-2’-deoxyuridine (BrdU), into the mixed cell suspension. This cellular response to the histocompatibility antigens that occurs in the MLR is also involved in cell-mediated immune responses within an individual and offered an in vitro correlate of cellular immune function. Standard MLR assays were performed in humans and most other animal species.The leukocyte subpopulations involved in the MLR were first characterized by using cells from neonatally thymectomized and bursectomized chickens. No MLR occurred when the Responder cells came from thymectomized animals, whereas bursectomized chicken leukocytes reacted in culture demonstrating that T-cells were the major cell type in Responder cell populations.
Originally, this assay was used to study possible donor — recipient incompatibilities for graft transplants to help predict better outcomes. However, the standard for graft matching now depends on a series of HLA-matching done with molecular typing methods.