Seriously though, there are clearly cells that can suppress immunity, autoimmunity or transplant rejection in many models. But, are these bona fide suppressors or just clever manipulators of the immune system? Practically, this does not matter, as the benefits are obvious, and the study of these approaches is highly commendable. But, to understand the immune system better, it is essential that we know the true nature of these elusive cells.

The term 'regulator' was initially substituted for 'suppressor' when the 'S' word was in its dark phase. Some bold scientists have again begun venturing to use this old term, now that things have been cleared up. The vast majority of researchers, however, describe their particular pet T cell as regulatory, when they really mean suppressive (but are hesitant to say so!). Their bias is often revealed by the suppressor-type assays that are used to detect T-cell function.

The real problem for us, however, is not that these researchers call their cells regulators when they mean suppressors, but that they actually think they are suppressors. We believe that in many cases, regulatory T cells are indeed regulators, or directors, of the immune response, rather than suppressors. For example, T helper 3 (T_H3) cells of the gut produce transforming growth factor-ß (TGF-ß), which inhibits the proliferation of other T cells in various assays. But, is this production of TGF-ß really to suppress T-cell proliferation, or is it to induce gut-associated B cells to isotype switch to immunoglobulin A? If the latter is the case, then the true function of T_H3 cells is regulation (of isotype switching) and not suppression. In this short viewpoint, we would like to suggest the possibility that there might not be a true natural suppressor T cell, but that other explanations, such as regulation of appropriate effector mechanisms or competition for homeostatic factors (see further reading by Barthlott et al.), might underlie the observed suppressive phenotypes of these cells.

References and links