For vaccines, CD4 ⁺ T cells can spell trouble The ideal vaccine elicits immune memory—either antibodies or memory T cells—to protect the host from subsequent infections. T cell–mediated immunity requires both helper CD4 ⁺ T cells and cytotoxic CD8 ⁺ T cells to kill virus-infected cells. But what happens when a vaccine only elicits CD4 ⁺ memory T cells? Penaloza-MacMaster et al. probed this question by giving mice a vaccine that generated only memory CD4 ⁺ T cells against lymphocytic choriomeningitis virus (LCMV). Instead of protecting mice against chronic LCMV, vaccinated mice developed massive inflammation and died. Virus-specific CD8 ⁺ T cells or antibodies protected mice from the pathology. These results may have implications for vaccines against chronic viruses such as HIV. Science , this issue p. 278