Nature Immunology pp 934 - 942

Sometimes too much 'help' can be a bad thing — at least for the immune system. In the September issue of Nature Immunology, Zinkernagel and colleagues describe a viral infection in which the antibodies that would effectively 'neutralize' a virus are drowned out by the large non-specific antibody response. They authors then turn this into a win-win situation: mice with fewer virus-specific T helper cells produced more antibodies that neutralize the virus, but the loss of 'help' doesn't seem to impede development of virus-specific killer T cells that are required to eliminate cells infected with the virus.

T helper cells provide cues to other cells of the immune system to ramp up their anti-viral defenses. However, as shown by the Swiss researchers, by activating too many T helper cells, non-specific antibody responses become predominant and delay the appearance of those capable of halting viral spread. This scenario of 'immune hypergammaglobulinemia' often accompanies the establishment of chronic infection, such as in HIV or hepatitis C viral infections. Using a mouse model of chronic infection against lymphocytic choriomeningitis virus, Recher et al. were able to reduce nonspecific antibody production and increase the abundance of neutralizing antibodies found in the blood by limiting T helper cell activation. The faster development of viral-specific antibodies also helped to prevent long-term viral persistence. Hence, intervention to limit, but not eliminate, T helper cell function might prove beneficial against pathogens that establish chronic infections.