Immune cells extracted from mice are an excellent research tool. Mice are often utilized as model species due to the functional similarity of many murine cell types to the corresponding human cells. Mouse immune cells provide great insight into the function of the human immune system. Mouse immune cells differ from human immune cells by only about 300 genes, making the genomes remarkably similar.
In both species, T cells play an integral role in immune response, specifically adaptive immunity. They accomplish this by expressing a surface receptor that can recognize antigens from pathogens, tumors, and environmental threats. T cells are also essential to immunological memory and immune tolerance.
Lymphocytes specifically drive adaptive immune response. Just as special surface receptors differentiate human T cell subsets, all classical mouse T cells express CD3 and can be subdivided into CD4+ (helper T cell) and CD8+ (cytotoxic T cell) subsets. Also similar to humans, mouse T cells circulate within the bloodstream and lymphatic system. Mouse T cells can also reside in secondary lymphoid organs, such as the spleen and Peyer’s patches within the mucous membranes of the intestines. T cells develop primarily within the thymus from the hematopoietic stem and progenitor cells that originate in the bone marrow.
Like T cells from other species, murine T cells navigate the body in an inactive naive state until they encounter their specific antigen. This activation triggers many effector immune responses that can cascade throughout the body depending on the trigger.
There are also significant differences between mice and humans that are taken into account, such as the expression level of specific surface markers. Lymphocytes are also found in a much higher concentration within the human bloodstream compared to a mouse, making the scale of murine T cell isolation considerably smaller. This causes mouse T cells to be isolated from other areas of high immune cell concentration, such as the thymus or spleen.
Mouse helper T cells express the coreceptor CD4 on their surface. These cells are called helper cells because the cytokines they produce provide critical signals to drive and coordinate the function of other immune cells. For example, mouse CD4+ T cell help is critical for many B cell responses, as the interaction of T cells and B cells can determine the isotype of antibody that the B cell produces. Highly concentrated within the spleen and lymph nodes of the mice, helper T cells make up nearly 25% of the cells in these immune organs. These cells can reveal how human immune cells communicate with one another and regulate immune responses, including important responses needed to clear unwanted pathogens as well as inappropriate responses to self-antigens that lead to autoimmune diseases.
Mouse cytotoxic cells express the coreceptor CD8 on their surface and, as in humans, are responsible for the direct cell-mediated killing of cancer cells or cells infected with pathogens. They can eliminate these aberrant cells by binding directly to their cell surface receptors. Successful attachment leads to killing the target cell through the release of effector molecules that can punch holes in the outer membranes of the target cells and induce cell death. This ability to directly kill target cells makes them of great importance to immunotherapy.
Mouse memory T cells can develop from both the CD4+ helper and CD8+ cytotoxic T cell subsets. Memory T cells are antigen-specific T cells that were created during an active immune response. While most of the responding cells are eliminated once the immune response is over and they are no longer needed, these cells remain in the bloodstream or lymphoid organs long after the infection has been eradicated. While T cells are known to respond strongly to their specific antigen and are capable of rapid replication, these characteristics are amplified when a familiar pathogen is encountered. This allows the body to launch an even faster and more robust immune response upon re-infection. Memory T-cells can be activated immediately upon recognition of the familiar pathogen, thus providing a much more rapid response compared to the primary infection.
Each type of immune cell has distinct surface receptors, allowing the microbubble technology to target each type. By creating specific antibody cocktails tailored around the known surface receptors on different murine immune cell types, the microbubbles can bind directly to and remove unwanted cells, leaving a population of untouched T cells ready for downstream processing.
A very high number of T cells is found within a mouse’s spleen, primarily due to the role the spleen has in immune response and regulation. T cells are equipped with various functions and can be distinguished by the specific markers expressed within the cell cytoplasm and on the cell surface. Understanding which T cells have which surface receptors can aid in their isolation.
T cells can also quickly proliferate during a response and signal other immune cells to do the same. This process is called T-cell expansion. During expansion, cells replicate at a very high rate, producing large numbers of cells expressing the same antigen-specific T cell receptor. This leads to a high number of active cells ready to fight the pathogen or tumor.
Mouse T cells provide an excellent and easily accessible source of T cells for studying immune cell function, and there are many protocols available to maximize the yield of in vitro T cell expansion. In an experimental setting, activation and expansion can be triggered in numerous ways using cells that have been isolated from murine splenocytes to better understand differentiation, antigen recognition, receptor signaling, cytokine production, and many other important aspects of the adaptive immune response.
Similar to human T cells, murine T cells are usually activated within secondary lymphoid organs such as the spleen or lymph node. The antigen is presented to the naive T cells by antigen-presenting cells (APCs) such as dendritic cells. If the antigen matches their T cell receptor, the cells will become activated. The APCs also provide additional signals to the T cells that supply information on the type of response required for the current invader. This murine T cell activation will simulate a full-scale immune response.
Once the T cells have received the required activation signals and instruction from the APCs, they then leave the secondary lymphoid organs and traffic to the site of infection, where they carry out their helper or cytotoxic effector functions.
Akadeum offers the most robust cell separation techniques for isolating murine T cells. Our microbubble technology in the Mouse T Cell Isolation Kit can also be used for separating other cell types from mouse and human blood sources. By negatively selecting cells of interest, the yield provided is high quality and pure, untouched by the separation protocol.
Learn more about the applications of Akadeum’s BACS™ for mouse T cells from spleen samples at our overview page, or explore other murine cell isolation kits available for purchase.