Antigen Presentation and T-Cell Activation in Epidermodysplasia Verruciformis

Cooper, Kevin D.; Androphy, Elliot J.; Lowy, Douglas R.; Katz, Stephen I.

doi:10.1111/1523-1747.ep12874631

Cited by 73 publications

(29 citation statements)

References 42 publications

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“…It is possible that the LFA-1 overexpression contributes to the lupuslike disease seen in this system. It is also interesting to note that the amount of UV light needed to inhibit DNA methylation and induce autoreactivity is approximately one-tenth that which causes a sunburn in Caucasians (31), supporting the hypothesis that UV light exposure in amounts frequently encountered by lupus patients could have an effect on their T cells. Finally, we have reported that patients with idiopathic lupus have impaired T cell DNA methylation (9, and that patients with active lupus have an autoreactive T cell subset identified by a relative overexpression of LFA-1, similar to 5-azaC-or PCA-treated cells (8).…”

Section: Discussionmentioning

confidence: 66%

Lymphocyte function—associated antigen 1 overexpression and t cell autoreactivity

Richardson

Powers²,

Hooper³

et al. 1994

Arthritis & Rheumatism

112

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Objective. To determine if DNA methylation inhibitors make T cells autoreactive by inducing lymphocyte function-associated antigen type 1 (LFA-1) ( C D l l d CD18) overexpression.Methods. T cell clones were treated with 3 distinct DNA methylation inhibitors or were stably transfected with a CD18 cDNA in a mammalian expression vector, and the effects on LFA-1 expression and activation requirements were examined.Results. LFA-1 overexpression, caused by DNA methylation inhibitors or by transfection, correlates with the development of autoreactivity.Conclusion. LFA-1 overexpression may contribute to T cell autoreactivity.

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Section: Discussionmentioning

confidence: 66%

Lymphocyte function—associated antigen 1 overexpression and t cell autoreactivity

Richardson

Powers²,

Hooper³

et al. 1994

Arthritis & Rheumatism

112

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“…Since S-100 stains a family of related calcium-binding proteins, they suggested that these proteins may be important in the function of Langerhans cells in HPV infection. In contrast to reports suggesting Langerhans cell functional deficits, Cooper and coauthors (30), studying lesions from patients with the HPV-related cutaneous disease epidermodysplasia verruciformis, reported that despite slight reductions in Langerhans cell number in lesions, as well as abnormal Langerhans cell morphology, isolated Langerhans cells appear to be functionally intact in their ability to present alloantigens to T cells.…”

Section: Adaptive Cell-mediated Immunitymentioning

confidence: 85%

“…Immunogenicity of nine of these potential antigenic epitopes for HLA-2.1 was tested (116). Using HLA-2.1 transgenic mice four immunogenic peptides were identified in vivo [E6 (29)(30)(31)(32)(33)(34)(35)(36)(37)(38), E7 (11)(12)(13)(14)(15)(16)(17)(18)(19)(20), E7 (82)(83)(84)(85)(86)(87)(88)(89)(90), and E7 (86-93)]. In addition, CTL induction of PBMC from humans confirmed immunogenicity, in vitro, of three of the four peptides [E7 (11)(12)(13)(14)(15)(16)(17)(18)(19)(20), E7 (82)(83)(84)(85)(86)(87)(88)(89)…”

Section: Adaptive Cell-mediated Immunitymentioning

confidence: 99%

Cell-Mediated Immune Response to Human Papillomavirus Infection

Scott

Nakagawa

Moscicki

2001

Clin Diagn Lab Immunol

234

217

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Acquisition of human papillomavirus (HPV) results in an infection of variable duration which may or may not be associated with clinically apparent lesions. Lesions caused by skintropic HPV types generally manifest as cutaneous warts and most often resolve over a period of months to years. On the other hand, anogenital infections are more likely to remain clinically inapparent. The development of DNA amplificationbased tests has demonstrated that anogenital infections are quite common and generally self-limited. For example, we and others have shown by PCR testing of multiple samples collected at different points in time-that 70 to 90% of sexually active adolescents and young women who develop an incident cervical HPV infection will show clearance of infection within 12 to 30 months (47,61,94). The factors influencing the natural history of these infections are not well understood. Given that persistent anogenital infection with oncogenic HPV types is associated with increased risk of neoplasia and invasive cancers (22,59,70,71,94,124) and that cervical carcinoma remains a leading cause of death among women in developing countries (129), understanding these factors is of considerable importance.Substantial effort has been directed recently at understanding the role of the host's immune response in the natural history of HPV, and in particular, anti-viral, cell-mediated immunity. Empirical evidence for the importance of cell-mediated immunity in control of HPV infection comes from an extensive body of literature documenting the increased prevalence of HPV infection and associated disease among immunosuppressed populations, including those with iatrogenic immunosuppression such as renal transplant recipients and individuals with human immunodeficiency virus (HIV) infection. Sillman and coauthors (128) reported in 1984 on 20 immunosuppressed women with various causes of immunosuppression who had lower genital neoplasia, describing evidence of associated HPV infection in all 20. Penn, in 1986, reported a 100-fold increase in cancer of the vulva and anus in renal transplant recipients (111). In the 1990s, as molecular testing for HPV infection came into its own, several reports confirmed increased incidence of HPV infection (50) and associated morbidities, including warts (77) and cervical squamous intraepithelial lesions (SIL) (104), among immunosuppressed renal transplant recipients.The most persuasive evidence for the association between cellular immune defects and HPV infection and related morbidities comes from persons with HIV infection. Such individuals show increased prevalence of anogenital HPV infection (31, 32, 60, 105-107) as well as longer periods of HPV persistence (31,40,46,90,136). In addition, infection with multiple HPV types and with oncogenic types are more common (9,31,46,78,90,107,136). Associations between markers of HIV disease status (e.g., viral load and CD4 lymphocyte count) and HPV infection have been inconsistent. Most studies have suggested that advanced disease and greater immunological ...

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“…The precise effector mechanisms leading to lesion destruction in these clinical infections, however, are unknown. Additional evidence for immune control of HPV infections includes the high incidence of active HPV disease in immunosuppressed patients (18,19,32,35,54).Despite the strong evidence of multiple mechanisms of Bcell and T-cell immunity to papillomavirus antigens in hosts with papillomavirus infections (reviewed in references 22 and 39), persistent infections are common. Cervical cancer associated with HPV accounts for over 250,000 deaths of women worldwide (42).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Combination Treatment with Intralesional Cidofovir and Viral-DNA Vaccination Cures Large Cottontail Rabbit Papillomavirus-Induced Papillomas and Reduces Recurrences

Christensen

Han²,

Cladel³

et al. 2001

Antimicrob Agents Chemother

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. However, recurrences at periods from 1 to 8 weeks after treatment cessation were observed at approximately 50% of cured sites. DNA vaccinations with CRPV E1, E2, E6, and E7 were initiated either after or at the time of intralesional treatments, and the recurrence rates were observed. When DNA vaccinations were started after intralesional cures, recurrence rates were similar to those of vector-vaccinated rabbits. A small proportion of recurrent sites subsequently regressed (4 out of 10, or 40%) in the vaccinated group versus no regression of recurrences in the vectorimmunized group (0 out of 19, or 0%), indicating partial effectiveness. In contrast, when DNA vaccinations were conducted during intralesional treatments, a significant reduction of recurrences (from 10 out of 19, or 53%, of sites in vector-immunized rabbits to 3 out of 20, or 15%, of sites in viral-DNA-immunized rabbits) was observed. DNA vaccination without intralesional treatments had a minimal effect on preexisting papillomas. These data indicated that treatment with a combination of antiviral compounds and specific immune stimulation may lead to long-term cures of lesions without the ensuing problem of papilloma recurrence.Treatment of persistent papillomas with intralesional and topical antiviral compounds and immunomodulators often leads to effective cure of treated lesions in clinical trials with human papillomavirus (HPV) disease (4,5,16,56). However, recurrences are common after treatment cessation (5,6,16,20,56). The reasons for clinical recurrences are unclear, but possible mechanisms include (i) reinfection at adjacent sites, (ii) incomplete destruction of the entire area of active clinical disease, (iii) reactivation of subclinical HPV disease in wounded areas within and adjacent to treated sites, (iv) incomplete activation or induced anergy of antigen-specific cell-mediated immunity to HPV-infected papilloma cells, and (v) genetic factors associated with ineffective host immunity together with antigenic differences between variants of the same HPV type (2,3,9,23,31,46,47,58).There is strong evidence that host immunity to papillomavirus antigens can clear the bulk of HPV and animal papillomavirus infections (reviewed in references 22 and 39). Spontaneous regression of papillomas induced by cottontail rabbit papillomavirus (CRPV), rabbit oral papillomavirus, bovine papillomavirus type 4, and canine oral papillomavirus in rabbits, cattle, and beagles have been observed (8,10,12,34,38,41). The regressions are associated with a heavy infiltrate of T cells of both CD4 and CD8 phenotypes (1,33,40), and regressions of all lesions occur systemically. Immunosuppression of animals during the periods of papilloma growth has been shown to prolong lesion persistence (29,37,48). HPV-infected lesion regression with an associated immune infiltrate and in situ detectable cytokines has been reported also (17,57). The precise effector mechanisms leading to lesion destruction in these clinical infections, however, are unknown. Additional evidence for immu...

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Antigen Presentation and T-Cell Activation in Epidermodysplasia Verruciformis

Cited by 73 publications

References 42 publications

Lymphocyte function—associated antigen 1 overexpression and t cell autoreactivity

Lymphocyte function—associated antigen 1 overexpression and t cell autoreactivity

Cell-Mediated Immune Response to Human Papillomavirus Infection

Combination Treatment with Intralesional Cidofovir and Viral-DNA Vaccination Cures Large Cottontail Rabbit Papillomavirus-Induced Papillomas and Reduces Recurrences

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