Detailed characterization of T cell responses to herpes simplex virus-2 in immune seronegative persons.
In 2003, we described a small cohort of subjects (n = 6) who possessed no detectable serum Abs to HSV-1 or HSV-2 and no clinical or virological evidence of mucosal HSV infection yet possessed consistently detectable HSV-specific T cell responses measured primarily by lymphoproliferative (LP) and CTL assays to whole HSV-2 Ag. We termed these persons immune seronegative (IS). This report characterizes the T cell responses in 22 IS subjects largely recruited from studies of HSV-seronegative subjects in ongoing sexual relationships with HSV-2-seropositive (HSV-2(+)) partners using pools of overlapping peptides spanning 16 immuno-prevalent HSV-2 proteins. Overall, 77% of IS subjects had HSV-specific LP responses, 85% had IFN-gamma ELISPOT responses to at least one HSV-2 peptide pool, and 55% had both LP and IFN-gamma ELISPOT responses. In some cases, IFN-gamma ELISPOT responses were in excess of 500 spot-forming cells per 10(6) PBMCs and persisted for over 5 y. Although HSV-2(+) subjects (n = 40) had frequent responses to glycoproteins and tegument and immediate-early (IE) proteins of HSV-2, T cell responses in IS subjects were directed primarily at UL39 and the IE proteins ICP4 and ICP0. These data suggest that the antigenic repertoire of T cells in IS subjects is skewed compared with that of HSV-2(+) subjects and that IS subjects had more frequent T cell responses to IE proteins and infrequent T cell responses to virion components. Understanding the mechanism(s) by which such responses are elicited may provide important insights in developing novel strategies for preventing acquisition of sexually acquired HSV-2.
Posavad
Christine M
CM
Vaccine and Infectious Disease Institute, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA 98109, USA. posavad@u.washington.edu
Remington
Michael
M
Mueller
Dawn E
DE
Zhao
Lin
L
Magaret
Amalia S
AS
Wald
Anna
A
Corey
Lawrence
L
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000097:blood; D002999:Clone Cells; D015331:Cohort Studies; D003601:Cytotoxicity Tests, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology / Q000635:transmission / Q000821:virology; D018258:Herpesvirus 2, Human / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012307:Risk Factors; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D055815:Young Adult
D000914:Antibodies, Viral; D018984:Epitopes, T-Lymphocyte