T helper Cell Suppression Improves Antiviral Response

By David Douglas

Activation of T helper cells (CD4 T cells) impairs the production of neutralizing antibodies in mice infected with lymphocytic choriomeningitis virus (LCMV), Swiss researchers report in an advance online publication of the September issue of Nature Immunology.

Suppression of T helper cell function improves virus neutralization.

This paradoxical outcome, lead investigator Dr. Mike Recher told Reuters Health, is due to the virus-neutralizing antibodies having "to compete with an overwhelming non-specific response," in this case, "polyclonal B cell activation and subsequent hypergammaglobulinemia."

Importantly, he added, "persistent human virus infections like HIV or HCV show similar signs of immune overactivation as in murine LCMV, including flu-like disease early after infection or the presence of hypergammaglobulinemia."

Dr. Recher of the Institute for Experimental Immunology, Zurich and colleagues demonstrated that in murine LCMV infection, both the specific and non-specific B cell response require the presence of CD4+ T help.

However, he continued, "by deliberately suppressing T cell help, specific antibody formation gets enhanced without suppressing the other key arm of the immune attack against viruses, namely CD8+ T cells or killer cells."

Thus, to avoid the immune system being misled into such overactivation, Dr. Recher concluded, "live vaccines deliberately suppressing early T helper cell activation are very promising candidates for vaccination against HIV or HCV."

08/13/04

Nat Immunol 2004.