T Cell Plasticity

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Science  15 May 2009:
Vol. 324, Issue 5929, pp. 857
DOI: 10.1126/science.324_857b

CD4+ T helper cells are important mediators of humoral immunity. Different types of infection induce distinct helper lineages with characteristic profiles of cytokine expression. During an infection, CD4+ T cells interact with B cells in lymph node follicles where, through cell-cell interaction and cytokine secretion, they determine the classes of antibodies that B cells produce. CD4+ T cells that induce B cell class switching, termed T follicular helper cells, express distinct phenotypic markers regardless of infection type and were thus thought to be a distinct lineage of helper cells; however, one lineage of cells can induce the different classes of antibodies associated with immune response to distinct classes of pathogens.

Three studies by Reinhardt et al., Zaretsky et al., and King and Mohrs address this issue in the context of a helminth infection, which generates a classical T helper cell 2 (TH2) immune response associated with interleukin-4 (IL-4) production. Using IL-4 reporter mice, the authors demonstrate that in the lymph node, most IL-4–producing T cells localize to B cell follicles. These cells are similar in phenotype to T follicular helper cells and are required for B cell class switching, but they also express TH2-associated genes such as GATA-3. In contrast, IL-4–producing cells outside of lymph nodes express TH2-associated markers, but not T follicular helper cell-associated markers. These studies suggest that T follicular helper cells may not represent a distinct lineage, but rather differentiate from other T helper cell lineages and help to channel B cell responses via the secretion of lineage-specific cytokines. These studies also provide insight into how humoral and cellular immunity are coordinated because the same helper cytokines that induce humoral responses in the lymph node also drive cell-mediated immunity in the periphery.

Nat. Immunol. 10, 385 (2009); J. Exp. Med. 206, 10.1084/jem.20090303; 10.1084/jem.20090313 (2009).

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