Regression of Canine Oral Papillomas Is Associated with Infiltration of CD4+ and CD8+ Lymphocytes

Abstract

Canine oral papillomavirus (COPV) infection is used in vaccine development against mucosal papillomaviruses. The predictable, spontaneous regression of the papillomas makes this an attractive system for analysis of cellular immunity. Immunohistochemical analysis of the timing and phenotype of immune cell infiltration revealed a marked influx of leukocytes during wart regression, including abundant CD4+ and CD8+ cells, with CD4+ cells being most numerous. Comparison of these findings, and those of immunohistochemistry using TCRalphabeta-, TCRgammadelta-, CD1a-, CD1c-, CD11a-, CD11b-, CD11c-, CD18-, CD21-, and CD49d-specific monoclonal antibodies, with previously published work in the human, ox, and rabbit models revealed important differences between these systems. Unlike bovine papillomavirus lesions, those of COPV do not have a significant gamma/delta T-cell infiltrate. Furthermore, COPV lesions had numerous CD4+ cells, unlike cottontail rabbit papillomavirus lesions. The lymphocyte infiltrate in the dog resembled that in human papillomavirus lesions, indicating that COPV is an appropriate model for human papillomavirus immunity.

Human Papillomavirus (HPV) Infection in Southern Africa: Prevalence, Immunity, and Vaccine Prospects

“…These infiltrating lymphocytes express the interleukin (IL)-2 receptor and the CD45 RO marker, respectively, indicating that they are both activated and antigen experienced. It is evident from the expression of the pro-inflammatory cytokines interferon (IFN)-γ , tumour necrosis factor (TNF)-α, and IL-12 that there is a T helper (Th) 1 dominant response in these regressing warts (29). B cells are noticeable by their absence, although other CD16 + APCs have been found in regressing lesions (30).…”

Hepatitis B Surface Antigen-based Vaccines for Human Neoplastic Disease

“…Regressing CRPV-associated warts have been reported to contain no CD4 + lymphocytes but do contain CD8 + lymphocytes (Selvakumar et al, 1997). This is in contrast to COPV (Nicholls et al, 2001), BPV (Knowles et al, 1996) and HPV (Coleman et al, 1994) lesions that all contain CD4 + lymphocytes, as well as CD8 + lymphocytes. Particularly in the BPV-4 model it has been reported that an increase in CD4 + cells correlates with regression of lesions, which also suggests important roles for CD8 + and γδ lymphocytes (Knowles et al, 1996).…”

“…As we were unable to detect E7HBE6 in mammalian cells, there may be a problem with expression from pE7HBE6 or on the other hand, E7HBE6 may induce stress and be degraded rapidly, which may enhance the CTL response (Nicholls et al, 2001;Cheng et al, 2003;Nakagawa et al, 2005). Using pE7HBE6 as a DNA vaccine and quantifying the CTL response …”

“…The application of pE7HBE6 as an anti cancer vaccine targeting oncoproteins E6 and E7 requires activation of a cytotoxic CD8 + T-cell response (Nicholls et al, 2001;Cheng et al, 2003;Ely et al, 2003;Turk et al, 2004;Nakagawa et al, 2005;Imai et al, 2008;Broom et al, 2010), which in turn requires activation of CD4 +ve APCs, DCs and macrophages (Chattergoon et al, 1998;Faiola et al, 1998;Stemberger et al, 2007;Masson et al, 2008). It has been demonstrated in a number of studies that "stressed cells" act as more efficient activators of CTL immune responses by more effective activation of DCs (Albert et al, 1998;Feng et al, 2002) and macrophages (Mills et al, 2000;Lleo et al, 2008;Zhou et al, 2009).…”

“…Therefore, incorporation of HPV-16 E6 and E7 into a fusion protein with HBsAg, delivered as a DNA or VLP vaccine may provide a vaccine antigen highly efficient at eliciting anti-tumour responses (Nicholls et al, 2001;Cheng et al, 2003;Nakagawa et al, 2005).…”