Antigen-specific CD8+ T cell subset distribution in lymph nodes draining the site of herpes simplex virus infection.
Inoculation with replicating virus leads to an increase in T cell numbers within lymph nodes that drain the site of infection. This increase has been associated with a nonspecific proliferation of bystander cells, with only a minority thought to be directed to the infectious agent. Such an assumption is largely based on precursor cytotoxic T lymphocyte (CTL) estimations using limiting dilution analysis. Recently, studies 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 investigation. We have defined T cell receptor sequences characteristic of CTL populations directed to a dominant determinant of the herpes simplex virus (HSV) glycoprotein B (gB). In this investigation, we used this receptor 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 consequence of HSV infection, the majority of these cells are small resting cells that are not enriched for gB-specific receptors. In contrast, a significant proportion of activated T cells are highly enriched for CTL bearing gB-specific receptors. Our results are therefore consistent with a nonspecific migration of CTL precursors into the lymph nodes draining the site of infection, followed by the activation and proliferation of the antigen-specific subset that normally makes up a small proportion of the naive T cell repertoire.
Cose
S C
SC
Department of Pathology and Immunology, Monash Medical School, Melbourne, Australia.
Jones
C M
CM
Wallace
M E
ME
Heath
W R
WR
Carbone
F R
FR
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002634:Chemotaxis, Leukocyte; D003602:Cytotoxicity, Immunologic; D019674:Genes, T-Cell Receptor beta / Q000235:genetics; D006561:Herpes Simplex / Q000276:immunology*; D007111:Immunity, Cellular; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000276:immunology; D016415:Sequence Alignment; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology
D000956:Antigens, Viral; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus