Overstimulated and ineffective

CD4⁺ T cells become ineffective if repeatedly stimulated through their T cell receptors (TCRs), according to a study by Jelley-Gibbs and colleagues on page 1101. The functional demise of these cells may help explain why persisting pathogens, such as Mycobacterium tuberculosis and HIV, are associated with ineffective CD4⁺ T cell responses during the chronic phase of infection.

Chronic infections have been shown to induce exhaustion or functional unresponsiveness in cytotoxic CD8⁺ T cells, but their effect on CD4⁺ T helper cells has not been well studied. Jelley-Gibbs et al. now show that repeated stimulation of CD4⁺ T cells generated effector cells that were more activated, based on the expression of activation markers CD69 and CD62L, than cells stimulated only once...