Characterization of the IFN-gamma T-cell responses to immediate early antigens in humans with genital herpes.
BACKGROUND
The IFN-gamma ELISPOT assay has been used to examine the T-cell repertoire for many disease states in humans but, as yet, not genital herpes. Using overlapping synthetic peptide libraries, an IFN-gamma ELISPOT assay was established that could measure CD4 and CD8 T-cell responses to HSV-2 antigens in patients with genital herpes.


RESULTS
In unexpanded T-cells isolated from peripheral blood, CD4 responses were readily measured against four immediate early antigens (ICP0, ICP4, ICP22 and ICP27), VP22 and gD. The CD4 responses were characterized by a low number of positive cells which produced large ELISPOTs. CD4 responses had a broad specificity and within individual patients several of the test antigens were recognized. In contrast, CD8 responses were found only in approximately 50% of patients and were typically specific to a single antigen. When disease status and immune responses were compared, an enhanced CD4 response to ICP4 in patients with a low recurrence rate was found. The ICP4 response was striking in three HSV-1 single positive genital herpes patients.


CONCLUSIONS
The survey of T-cell responses is an important step to understand the host cellular immune response in individuals with genital herpes. The assay described here has the capability of measuring CD4 and CD8 T-cell responses that may be used to correlate disease status with specific immune responses. In an evaluation of 18 subjects a trend of positive responses to an immediate early protein, ICP4, was found in individuals that had a low rate of disease recurrence.
Braun
Ralph P
RP
Wyeth Vaccine Research, 401 North Middletown Rd. Pearl River, NY, USA. braunr@wyeth.com
Payne
Lendon G
LG
Dong
Lichun
L
D000328:Adult; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000276:immunology* / Q000472:pathogenicity; D018258:Herpesvirus 2, Human / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
D000956:Antigens, Viral; D017874:Immediate-Early Proteins; C048925:herpes simplex virus, type 1 protein ICP4; D007371:Interferon-gamma