We’ve discussed white blood cells before.
Whether you look at tumor-infiltrating lymphocytes, marrow-derived natural killer (NK) cells, or chimeric antigen receptor (CAR) T-cells, lymphocytes in general have many different therapeutic applications that are currently being researched, especially in the field of oncology. However, these are all the more aggressive parts of the immune system, and even among a subclass as specific as T-cells, there are several other functions that we haven’t touched on.
Last time, on the Amazing Sample blog series, we discussed CNF and neural tissue. This time, let’s break down some of the ways T-cells can be amazing samples in their own right.
The Helper’s Lament
Most people learn in school about the CD4+ “helper” T-cell (Th), but only in one context – it is the usual targeted victim of HIV. Their nickname comes from how their indirect function, activating or assisting the active immune response, and compromising them is what makes HIV infections so resilient and effectively invisible to the immune system. While we have developed antiretroviral therapies that can substantially extend the life expectancy of an infected individual, this does not put much of a dent in the hidden reserves of virus hidden away inside the already infected cells.
Last January, though, a group of researchers at Rockefeller University found some interesting data on the virus’s functionality. Through using a computational method developed by one of their research associates, they analyzed CD4 T-cell samples from 13 HIV+ individuals on antiretroviral regimens, in order to observe the specific sites of the human genome the viral genetic material had inserted itself. By assuming a negligible probability of two different cellular infections having the same insertion site, they were able to ascertain the frequency of cells that had managed clonal expansion after infection, as compared to the single-occurrence “unique” integration sites. What they discovered is that, of the 75 clonal viral sequences, none of them were viable for production of the virus. The research’s implication is that those unique integration sites might hold the secret of the viral reservoir, and accordingly be a future target for antiviral therapies. Read their research published in Cell here.
Even more exciting, later in the year, a different group of researchers at the NIH developed a therapy that could actually identify and eliminate cells containing the latent, inactive virus. Through use of a bispecific immunomodulatory protein, targeting both CD3 and CD8, they were able to not only stimulate expression of the latent proviral genes, but alert the rest of the immune system to these infected cells and induce lysis. This treatment seems quite promising, and could be key to diminishing---if not eliminating---viral material in infected individuals. Read their research published in Nature here.
Regulators, Mount Up!
Another class of T-cells are the regulators cells (Treg), which regulate the rest of the immune system, telling them when to lessen or halt their activity. We’ve known about these cells for awhile, and answer some obvious questions, as to how our immune systems do not have allergic reactions to every new food we eat, or how mothers’ immune systems don’t usually attack their children during pregnancy. For a more in-depth discussion on the general functioning and other traits of Treg cells, check out this article from the Scandanavian Journal of Immunology.
Treg cells are a clear target for treatment of autoimmune diseases and transplant rejection in general – if not because of mutation or something else crippling the regulatory cells, then perhaps because introducing more Treg cells would overcompensate for whatever is aggravating the immune system. Unfortunately, while Treg infusions have been proven quite efficacious in preclinical data, there are many challenges and difficulties with scaling manufacture to clinical and commercial levels.
However, there have been some steps to show that there are other methods which might help provide a more curative solution to individuals with such issues – a twist on allergic desensitization. If you’ve never had an allergy shot yourself, effectively the immune system can be taught to tolerate allergens if they are introduced in slowly increasing amounts, effectively teaching the Treg cells that they should not be targeted and accordingly that the immune system might need suppression. As clear as the parallel might seem in retrospect, no one had seriously tried applying the same technique to autoimmune disorders, until researchers at Bristol University did recently. They found that, while the dose escalation must be controlled, self-antigen doses can actually help teach an autoimmune system to suppress the erroneous reaction. This research might lead to developing a more permanent remedy to any such afflictions – even if it requires an escalating dose, this would be more lasting than requiring multiple Treg infusions, or the therapies that are the current standard of care.
Even when looking at the ancillary cells of the immune system, rather than the macrophages and NK cells, there is a wealth of opportunity both in researching and understanding the system’s mechanisms, and in developing therapies to treat various immune-related diseases. Truly, T-cells can be an Amazing Sample.
Do you work with T-cells in your research? Please, share your story and comment below!
To learn more about the important variables to consider if you have a cell-based therapy in development and the unique logistical challenges associated with autologous cell therapies, please download our eBook Cell Therapy Logistics: Beyond the Basics.