What is a Mixed Lymphocyte Reaction?

In short, Mixed Lymphocyte Reactions (MLR’s) are cell proliferation assays. There are a few main types of MLR’s (one-way, two-way, and three-way), and many different ways to set them up so that they meet a scientist’s or organization’s guidelines, as well as the regulatory guidelines that they must follow. In an effort to keep this guide simple, we will only discuss the two main types of MLR’s. First, a quick background on the concepts of MLRs.

Background on Mixed Lymphocyte Reaction

Lymphocytes are type of white blood cell and are one of the most essential components for your body’s immune response. Unlike the cells of our innate immune system which can only respond to a limited number of infection types, the majority of lymphocytes act as part of our adaptive immune system and can quickly identify, adapt, and fight any new type of infection if given enough time. Additionally, lymphocytes of the adaptive immune system remember infections and respond more quickly and with a stronger response if that type of infection is encountered again in the future. Understanding how our adaptive immune system works is critical when developing new therapies and treatments against ever-mutating viruses, new diseases, medical conditions, and types of cancer. Mixed Lymphocyte Reactions (MLRs) are great assays to help us understand how these newly developed compounds interact with our immune cells, and can provide researchers valuable information on the mechanism of action, efficacy, and safety of their product. Check out our main Mixed Lymphocyte Reaction page for example MLRs.

Mechanism of a Mixed Lymphocyte Reaction

Simply put, MLRs are comprised of at least two unique cell populations (lymphocytes) mixed together in a co-culture. This causes a cell-mediated inflammatory response as each lymphocyte population will identify the other population of lymphocytes as “non-self” and begin to mount a response to clear the foreign invader. Using this as a model of an inflammatory response, we can now add drugs, biomaterials, cells, or other therapeutic products to observe how these materials enhance, suppress, or otherwise alter the inflammatory response to produce a specific desired outcome. To test a therapeutic products immunogenicity (the innate ability to cause an inflammatory response), one of the lymphocyte populations can be removed, so that the only interaction we observe is of one lymphocyte population against the therapeutic product. Both of these MLR methods are a great way to test the efficacy and the safety of a new therapeutic product with human cells prior to performing human clinical trials. Check out more details of why mixed lymphocyte reactions are performed.

One vs Two-way Mixed Lymphocyte Reactions

There are several possible variations of an MLR. In a one-way MLR, one population of lymphocytes act as a stimulator and another population of lymphocytes as a responder. The stimulator lymphocytes are rendered to a non-proliferative state either by drug treatment or irradiation, to prevent them from proliferating or from mounting an immune response. Therefore, when the MLR is analyzed, the only lymphocyte activity will be from the responder group.

In a two-way MLR both populations of lymphocytes act as responders and stimulators against each other. Two-way MLRs provide a basic understanding of how a therapeutic product affects lymphocytes, while a one-way MLR provides greater detail on the effects in one lymphocyte group and account for differences between the stimulator and responder lymphocyte populations (such as allogeneic donor variation if cells are from two different human donors). Read more about how to perform a mixed lymphocyte reaction and how to optimize mixed lymphocyte reaction.

In a nutshell, MLR’s are pretty much what they sound like; mixing populations of lymphocytes together, and measuring the reaction that occurs. In a one-way MLR, only one lymphocyte population can respond or proliferate. In a two-way MLR, both populations can proliferate. Now that we’ve established what a Mixed Lymphocyte Reaction is, let’s see why anybody would perform one!

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