ANTIGEN-SPECIFIC CD8(-CELL SUBSET DISTRIBUTION IN LYMPH-NODES DRAINING THE SITE OF HERPES-SIMPLEX VIRUS-INFECTION() T)

Inoculation with replicating virus leads to an increase in T cell numb ers within lymph nodes that drain the site of infection. This increase has been associated with a nonspecific proliferation of bystander cel ls, with only a minority thought to be directed to the infectious agen t. Such an assumption is largely based on precursor cytotoxic T lympho cyte (CTL) estimations using limiting dilution analysis. Recently, stu dies using more advanced molecular approaches have suggested that such functionally derived precursor frequencies considerably underestimate the proportion of T cells specific for the antigen under investigatio n. We have defined T cell receptor sequences characteristic of CTL pop ulations directed to a dominant determinant of the herpes simplex viru s (HSV) glycoprotein B (gB). In this investigation, we used this recep tor signature as a probe to directly monitor changes occurring within lymph nodes draining the sites of active infection with HSV. We found that although lymph node CD8(+) T cell numbers increase as a consequen ce of HSV infection, the majority of these cells are small resting cel ls that are not enriched for gB-specific receptors. In contrast, a sig nificant proportion of activated T cells are highly enriched for CTL b earing gB-specific receptors. Our results are therefore consistent wit h a nonspecific migration of CTL precursors into the lymph nodes drain ing the site of infection, followed by the activation and proliferatio n of the antigen-specific subset that normally makes up a small propor tion of the naive T cell repertoire.