These studies provide evidence that the strength of the TCR signal can play a direct role in directing the extent of

both thymocyte deletion and Treg-cell differentiation, and suggest that distinct TCR signaling thresholds and/or pathways can promote CD4SP thymocyte deletion versus Treg-cell formation. “
“In June this year, it was 30 years since the identification of the first AIDS patient (see the review in this issue 1). Despite rapid responses JNK signaling pathway inhibitors by scientists and doctors to understand this disease in both clinical and experimental systems 2, 3, human immunodeficiency virus type 1 (HIV-1), the causative agent of AIDS (Fig. 1), continues to feature among world’s three major killers destroying millions of lives, families and communities. More than 30 drugs have been developed just for HIV-1 and there have been three successful trials showing their impressive preventive potential. However, because of the drug unavailability, particularly in resource Selleck MK 1775 poor settings, side effects and potential development of resistance, the best hope for a profound fall in the incidence of HIV-1 infection remains the development of an effective prophylactic HIV-1 vaccine. Here, we discuss

T-cell vaccine designs mainly, briefly mentioning antibody vaccines. Even if a vaccine that actively stimulates broadly neutralizing antibodies (bNAbs) can be made 4, it will be hard to stop some HIV-1 infection occurring (e.g. through cell–cell transmission) and T-cell-mediated

immune responses to control infection will be required. T cells function by killing HIV-1-infected cells and producing soluble factors that can directly and indirectly control HIV-1 spread. While T cells cannot prevent the transmitted virus from infecting host cells, potent vaccine-induced HIV-1-specific T-cell responses could increase the dose of incoming virus necessary to establish infection (i.e. decrease acquisition) Liothyronine Sodium 5, limit the extent of viral replication during primary viremia (i.e. reduce tissue damage), lower the virus load at set point (i.e. reduce further virus transmission) and slow the rate of CD4+ T-cell decline (i.e. delay the development of AIDS). The simian immunodeficiency virus/macaque challenge model strongly supports this view, showing that potent T-cell responses alone can lower virus load and delay the development of AIDS 6–8. Thus, ideally, a successful HIV-1 vaccine will induce both T-cell and antibody responses; however, an effective T- or B-cell vaccine alone is nonetheless likely to impact the epidemic 9. Scientists developing HIV-1 vaccines face a long list of challenges. Although these differ for the induction of effective T-cell responses in comparison with induction of the desired bNAb specificity by active immunization, one major hurdle is common, namely the extreme HIV-1 variability.