Tiliqua rugosa—also known as the sleepy lizard—is a gorgeously chunky species, part lizard and part pinecone in appearance, which is found across the southern half of Australia. But it’s what’s on the inside that has captured the attention of researchers. Reptiles in general have immune systems that are unusual from a mammalian perspective; for example, they may rely more heavily on innate immunity and less on adaptive immunity, says University of New Mexico biologist Rob Miller. But the sleepy lizard (along with other scaled reptiles, a group known as squamates), may be even stranger.
Last month, Miller and an international team of scientists published a study in the Journal of Immunology comparing the sleepy lizard’s genome to that of the tuatara (a lizardlike animal that is the closest living relative of the squamates). The work revealed something strange: large deletions in the lizard’s genome resulted in the removal of genes necessary to produce γδ T cells, an important part of the immune system in most vertebrates. γδ T cells are so named because they have receptors made of a γ segment and a δ segment; these receptors allow the T cell to recognize specific antigens.
This work is helping to fill a massive gap in our knowledge. In terms of immunology, says Miller, “reptiles are a group of vertebrates that we know almost nothing about.”
The implications of the loss of this subset of T cells for lizards and snakes is not entirely clear, as the function of γδ T cells is not completely understood. “γδ T cells are really still quite enigmatic,” says Laura Vogel, an immunology researcher at Illinois State University whose research includes turtles and who was not involved in the sleepy lizard study. “We don’t understand a lot about their normal function, even in humans.” However, some evidence indicates that these cells may play important roles in wound healing, immune surveillance in the skin and mucous membranes, and the response to certain types of infections, and that they may have both tumor-promoting and antitumor effects.
Yet despite this loss of a major section of the immune system, the squamates are a very successful group. “Squamates consist of around ten thousand species,” says Miller. “And that ranges from sea snakes to horny toads [a type of lizard] living out in the middle of the desert. They’ve filled a wide niche on this planet.”
Even though snakes and lizards don’t have γδ T cells, they clearly still need to do things such as healing wounds and protecting themselves from infection. “So now the question is: how do they compensate for not having [γδ T cells]?” says Miller.
Miller and the team wanted to see if squamates’ remaining set of T cells, known as αβ T cells, might be more diverse, with a greater variety of “flavors” of αβ T cell receptors, which are used to recognize different types of antigens, in make up for the missing γδ T cells. But when they examined the genes that encoded components of α and β T cell receptors in the sleepy lizard, they found that these genes weren’t any more complex than the α and β T cell receptor genes in the tuatara, a species that has γδ T cells.
However, Miller says it’s too soon to completely rule out αβ T cells compensating for γδ T cell loss—future studies could examine whether there is any functional compensation by determining if αβ T cells show up in tissues like the skin, where one would normally expect γδ T cells.
Miller says another possibility is that squamates’ innate lymphoid cells—which, as the name suggests, are part of the innate immune system, not the adaptive system as T cells are—may take over some of the roles traditionally performed by γδ T cells.
Laura Zimmerman, a biologist at Millikin University in Illinois who was not involved in Miller’s study, agrees that the innate immune system may play a compensatory role, and also emphasizes the importance of future studies on immune cell function. “When it comes to squamates, a lot of the information we have comes from genetic studies like this one. But even compared to other reptiles, we have fewer functional immune assays, so I don’t think we have a clear picture of what their immune system is actually doing.”
Vogel says that studying reptilian immune systems may be beneficial for future conservation efforts. Such work, she says, could help experts to “better intervene in cases of say, an endangered species where we might need to design a vaccine or think about a treatment for a particular disease.” Potential conservation implications are especially salient for squamates given a recent analysis that revealed that more than 20 percent of reptile species are currently threatened.
It’s an open question whether or not squamates might be more susceptible to certain types of diseases than other reptiles that still possess γδ T cells, Zimmerman says.
Overall, Vogel says that these new findings are intriguing. “It would be great if we had more information on a wider array of reptiles,” she says. “We really need to support this kind of research on nonmodel species.”
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