Quantitative analysis of adenovirus-specific CD4+ T-cell responses from healthy adults.
Although nearly all adults are seropositive for adenoviruses, little is known about the cellular immune responses to these ubiquitous pathogens. We have previously identified adenovirus-specific proliferative T-cell responses in peripheral blood mononuclear cells (PBMC) from healthy adults. In this study, memory T-cell responses to adenovirus were further evaluated in healthy adult donors using a short term, quantitative enzyme-linked immunospot assay (ELISPOT) assay. Adenovirus antigen induced specific secretion of interferon-gamma (IFN-gamma) from PBMC within 12 hours of incubation. PBMC from 20 of 22 healthy donors (90.9%) expressed IFN-y in response to adenovirus. Responder cells were identified as CD4+ T cells by immunomagnetic depletion methods. Interleukin-4 (IL-4) secretion was not detected, consistent with a TH1 response. There was a 10-fold variation in the frequencies of adenovirus-specific CD4+ T cells between donors (range, 34 to 294; median, 122 per million PBMC). Adenovirus-specific T cell frequencies remained stable over periods up to 2 years among individual donors, but there was an inverse correlation between frequency and donor age. These quantitative data suggest that most adults retain adenovirus-specific cellular memory after childhood exposure. This assay may be useful for the evaluation of adenovirus-specific CD4+ T-cell responses in patients treated with adenovirus gene therapy vectors and the identification of major T-cell epitopes.
Olive
M
M
Department of Medicine, Center for Human Virology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Eisenlohr
L C
LC
Flomenberg
P
P
D000260:Adenoviruses, Human / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D008875:Middle Aged; D013997:Time Factors; D015678:Viral Structural Proteins / Q000276:immunology
D000956:Antigens, Viral; D015678:Viral Structural Proteins; D015847:Interleukin-4; D007371:Interferon-gamma