Lee K. Roberts

In order to assess the usefulness of haptoglobin as a measure of the acute phase response in cattle, the concentration of serum haptoglobin was estimated in the non-infectious conditions of milk fever and ketosis, and in the infectious conditions of severe mastitis, acute severe metritis, retained placenta and chronic endometritis. Mean haptoglobin concentrations were normal in cattle with non-infectious conditions and chronic endometritis but significantly increased in cattle with infectious conditions.

Our study was designed to analyze the possible involvement of prostaglandins in the mechanisms responsible for the depressions in contact hypersensitivity (CH) responsiveness observed in UVR-exposed animals. Low-dose UVR-exposed animals were found to exhibit a depressed capacity to elicit CH responses after hapten application to irradiated (devoid of Langerhans cells) or UVR-protected (normal Langerhans cells) dorsal skin surfaces. Normal responsiveness was observed in low-dose UVR-exposed animals sensitized through unirradiated ventral skin surfaces. Indomethacin treatment of low-dose UVR-exposed animals (to inhibit prostaglandin synthesis in vivo) caused a retention in the capacity to respond normally to CH induction to haptens applied to the nonirradiated, but not to irradiated, dorsal skin surfaces. High-dose UVR-exposed animals, which normally exhibit a depression in responsiveness to hapten sensitization, retained a normal capacity to elicit CH responses if treated with the drug indomethacin. These findings implicate prostaglandins in the pathogenesis of the immunologic hyporesponsiveness, observed in low- and high-dose UVR-exposed animals. Our studies also determined that under all experimental conditions where animals were contact sensitized through nonirradiated skin sites, CH-effector cells could be found in the draining lymph nodes. No CH-effector cells were observed in the lymph nodes of mice that were contact sensitized directly through irradiated skin sites. It was also found that the spleens of both UVR-exposed and normal animals contained adoptively transferrable suppressor cells subsequent to hapten application. This demonstration of CH-effector and CH-suppressor cells in both normal and UVR-exposed animals did not directly relate to the potential of the donor animals to elicit a CH response.

An automated method for the estimation of the acute phase protein haptoglobin was developed and used to compare the blood haptoglobin concentrations of 42 sheep examined post mortem with other haematological findings in infectious and non-infectious conditions. Haptoglobin was also assayed in 863 sheep from nine apparently normal flocks; of these sheep seven per cent had significantly raised haptoglobin levels. The studies showed that haptoglobin was useful as a marker for the presence of bacterial infection in sheep, and was more sensitive, specific and efficient and less likely to give false positive and negative results than a haematological examination.

Efforts aimed at restoring robust immune responses limiting human immunodeficiency virus (HIV)-1 replication therapeutically are warranted. We report that vaccination with dendritic cells generated ex vivo and loaded with HIV lipopeptides in patients (n = 19) on antiretroviral therapy was well tolerated and immunogenic. Vaccination increased: (i) the breadth of the immune response from 1 (1-3) to 4 (2-5) peptide-pool responses/patient (p = 0.009); (ii) the frequency of functional T cells (producing at least two cytokines among IFN-γ, TNF-α, and IL-2) from 0.026 to 0.32% (p = 0.002) and from 0.26 to 0.35% (p = 0.005) for CD4(+) and CD8(+) T cells, respectively; and (iii) the breadth of cytokines secreted by PBMCs upon antigen exposure, including IL-2, IFN-γ, IL-21, IL-17, and IL-13. Fifty percent of patients experienced a maximum of viral load (VL) 1 log10 lower than the other half following antiretroviral treatment interruption. An inverse correlation was found between the maximum of VL and the frequency of polyfunctional CD4(+) T cells (p = 0.007), production of IL-2 (p = 0.006), IFN-γ (p = 0.01), IL-21 (p = 0.006), and IL-13 (p = 0.001). These results suggest an association between vaccine responses and a better control of viral replication. These findings will help in the development of strategies for a functional cure for HIV infection.