Helper T (Th) cell identity may not be for life. According to a pair of studies from Zaretsky et al. (page 991) and King and Mohrs (page 1001), Th2 cells can turn into follicular T cells when duty calls.
Many immunologists consider each Th cell subset to be its own distinct class. The same is true of follicular T cells, CD4+ cells found in the B cell follicles and germinal centers of lymph nodes. Yet here, two independent research teams found that Th2 cells morph into follicular T cells in response to worm infections. “What we previously believed to be rigid effector T cell compartments might in fact be rather plastic,” says Edward Pearce, senior author of the Zaretsky et al. study.
The consensus has been that Th2 cells respond to worm infections by making IL-4, which helps B cells produce protective antibodies. Now these groups report that lymph node Th2 cells, which express IL-4 and GATA-3 like bona fide Th2 cells, gain follicular T cell attributes in response to parasitic worm infections. In addition to their follicular location, the cells expressed defining characteristics of follicular T cells, including IL-21, CXCR5, and ICOS.
Follicular T cells and B cells relied on one another. The T cells that expressed follicular T cell markers weren't found outside of the follicle and, according to Zaretsky et al., their development from Th2 precursors depended on intact germinal centers. King and Mohrs show that antibody synthesis in response to a worm infection was impaired in the absence of follicular T cells and the IL-4 they produced.
The ability to become a follicular T cell may not belong to Th2 cells alone. A study recently published in Nature Immunology showed that follicular T cells expressed either IL-4 or the Th1 cytokine IFN-γ in a setting designed to trigger a mixed Th1/Th2 response.
The classical rule is that Th2 cells promote IgG1 and IgE production by secreting IL-4, and Th1 cells promote IgG2 production with IFN-γ. These new data suggest that it may instead be the follicular helper T cells derived from either Th1 or Th2 cells that drive the production of certain B cell antibody isotypes.
It remains unclear whether other effector T cell subsets can metamorphose, and whether follicular T cells can leave the lymph node and return to their Th2 origins.