The changes in insulin resistance seen after gastric bypass, which are responsible for the resolution or improvement of type 2 diabetes occur within 6 days of the surgery, before any appreciable weight loss has occurred. This finding has implications for our understanding of the mechanism of insulin resistance in severely obese patients and is consistent with a humoral mechanism emanating from the GI tract.

The first 200 N-terminus amino acids of the L2 capsid protein of BPV-4 (designated L2a) are an effective prophylactic vaccine against BPV-4 infection. Vaccination with L2a induces the production of virus neutralizing antibodies, and when L2a antibodies are removed from immune sera, the sera lose their neutralization activity. L2a encodes three dominant B-cell epitopes, defined as epitope 1 (amino acids 101-120), epitope 2 (aa 131-151), and epitope 3 (aa 151-170). To investigate whether any of these epitopes are responsible individually or in combination for protection against viral challenge, synthetic peptides, corresponding to the three epitopes (peptides 11, 14, and 16, respectively) and conjugated to keyhole limpet hemocyanin (KLH) were tested in vaccination challenge experiments. Calves vaccinated with the three peptides together showed no evidence of papillomavirus infection; those vaccinated with peptide 14 alone developed only early lesions which did not progress to proper papillomas and regressed rapidly; those vaccinated with peptide 11 or peptide 16 alone were not protected and proceeded to develop papillomas. Therefore the three B-cell epitopes are not conventionally "neutralizing" when presented individually, but in combination they form a complex neutralization domain, and, in particular, epitope 2, represented by peptide 14, encodes a domain responsible for disease prevention.

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Papillomavirus-induced lesions often regress spontaneously in both humans and animals. Papilloma regression is deemed to be due to a cell-mediated immune response, the nature of which is still ill defined, and is accompanied by immune cell infiltrates. To gain further information on the nature and role of the immune cells present in regressing papillomas, we have analyzed biopsies of papillomas induced in the soft palate of cattle by bovine papillomavirus type 4 (BPV-4) and have phenotypically characterized and quantified the lymphocytes present in these lesions. Eleven papilloma biopsies and seven biopsies of noninfected palate were analyzed for the presence of activated CD4 ؉ , CD8 ؉ , and ␥␦(WC1 ؉ ) lymphocytes. We found large numbers of lymphocytes in the subepithelial derma of papillomas but not in normal palate tissue; these cellular masses consisted predominantly of CD4 ؉ lymphocytes, with only a few CD8 ؉ and ␥␦(WC1 ؉ ) lymphocytes, generally positioned at the periphery of these masses. All three subtypes of lymphocytes were found interdigitated with the cells of the basal layer both in papillomas and in normal palate tissue, but while basal layer CD8 ؉ and ␥␦(WC1 ؉ ) T cells were detected with similar frequencies in papillomas and uninfected palate, basal layer CD4 ؉ T cells were much more frequent in papillomas. CD4 ؉ , CD8 ؉ , and ␥␦(WC1 ؉ ) lymphocytes were found in the suprabasal layers of papillomas, but the CD8 ؉ and ␥␦(WC1 ؉ ) T cells were more numerous and had migrated further into the differentiating keratinocytes of the papilloma fronds than the CD4 ؉ T cells. We conclude that T-cell infiltration is characteristic of regressing BPV-4 papillomas, that CD4 ؉ lymphocytes are specifically and massively recruited into the regressing papillomas, and that although all three lymphocyte subsets can penetrate the papilloma, only the CD8 ؉ and ␥␦(WC1 ؉ ) lymphocytes are able to migrate into the fronds. These results suggest that all three lymphocyte subsets have an important role to fulfill during natural regression of papillomas.

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