1. Howard Hughes Medical Institute, Departments of Medicine and Microbiology/Immunology, University of California San Francisco, San Francisco, California 94143-0654, USA
2. Present address: Trudeau Institute, Saranac Lake, New York 12983, USA.

Correspondence to: Richard M. Locksley Correspondence and requests for materials should be addressed to R.M.L. (e-mail: Email: locksley@medicine.ucsf.edu).

Abstract

Type-2 immunity requires orchestration of innate and adaptive immune responses to protect mucosal sites from pathogens. Dysregulated type-2 responses result in allergy or asthma¹. T helper 2 (T_H2) cells elaborate cytokines, such as interleukin (IL)-4, IL-5, IL-9 and IL-13, which work with toxic mediators of innate immune cells to establish environments that are inhospitable to helminth or arthropod invaders². The importance of T_H2 cells in coordinating innate immune cells at sites of inflammation is not known. Here we show that polarized type-2 immune responses are initiated independently of adaptive immunity. In the absence of B and T cells, IL-4-expressing eosinophils were recruited to tissues of mice infected with the helminth Nippostrongylus brasiliensis, but eosinophils failed to degranulate. Reconstitution with CD4 T cells promoted accumulation of degranulated IL-4-expressing cells, but only if T cells were stimulated with cognate antigen. Degranulation correlated with tissue destruction, which was attenuated if eosinophils were depleted. Helper T cells confer antigen specificity on eosinophil cytotoxicity, but not cytokine responses, so defining a novel mechanism that focuses tissue injury at sites of immune challenge.