Inhibition of interleukin‐2 by a Gram‐positive bacterium, Streptococcus mutans

SUMMARY Generation ofan effective cellular immuneresponseiskeytothesuccessful development ofboth humoral andcellular immunedefences against mostpathogens. However, whilethetypeof cellular immuneresponseelicited byany given pathogen isdictated bytheentire arrayofantigens andmolecules whichcomprise thatpathogen, moststudies ofhumanimmuneresponsesto bacterial pathogens tendtofocus on selected antigens. Thisisa result, inpart,ofa desire tofind those antigens thatwill generate a desired immuneresponse,as well as limited technology for monitoring thecomplex arrayofresponsesgenerated byan intact organism. Utilizing Streptococcus mutansas a modelGram-positive organism, a novelflowcytometric assay thatpermits the identification ofindividual cells within a responding population, andhighly sensitive cytokine assays,we showforthefirst timethatCD8Tcells andnatural killer (NK)cells comprise a significant componentoftheresponsetothis organism inhumans. Thisisdespite thefact that CD8Tcells are traditionally thought torespond toendogenously derived antigens only. In addition, we provide thefirst evidence thata Gram-positive organism can actively inhibit interleukin-2 (IL-2), an important autocrine growthfactor forTcells. Thelatter observation could represent an additional mechanism bywhichGram-positive organisms evadehostdefences.