Rat Anti-Mouse CD4 Monoclonal antibody, clone YTS 191 Functional Grade

The immunodeficiency observed in HIV-1-infected patients is mainly due to uninfected bystander CD4(+)T lymphocyte cell death. The viral envelope glycoproteins (Env), expressed at the surface of infected cells, play a key role in this process. Env triggers macroautophagy/autophagy, a process necessary for subsequent apoptosis, and the production of reactive oxygen species (ROS) in bystander CD4(+)T cells. Here, we demonstrate that Env-induced oxidative stress is responsible for their death by apoptosis. Moreover, we report that peroxisomes, organelles involved in the control of oxidative stress, are targeted by Env-mediated autophagy. Indeed, we observe a selective autophagy-dependent decrease in the expression of peroxisomal proteins, CAT and PEX14, upon Env exposure; the downregulation of either BECN1 or SQSTM1/p62 restores their expression levels. Fluorescence studies allowed us to conclude that Env-mediated autophagy degrades these entire organelles and specifically the mature ones. Together, our results on Env-induced pexophagy provide new clues on HIV-1-induced immunodeficiency.

Alemtuzumab (anti-CD52 mAb) leads to a long-lasting disease activity suppression in patients with relapsing forms of multiple sclerosis (MS). In this study, we examined the change of the immune cell repertoire and the cellular reactivity after treatment with alemtuzumab. We analyzed the number of IFN-gamma-secreting cells in presence of several peptides which had been eluted from the central nervous system (CNS) of MS patients and are possible targets of autoreactive T cells in MS. The patients showed a stabilized disease activity measured in clinical parameters and lesion formation after the treatment. We detected a reduction of the number of IFN-gamma-secreting cells in the presence of every tested self-antigen. The number of IFN-gamma-secreting cells was also reduced in the presence of non-self-antigens. We also found a clear change in the immune cell repertoire. After an almost complete depletion of all lymphocytes, the cell specificities showed different reconstitution patterns, resulting in different cell fractions. The percentage of CD4+ T cells was clearly reduced after therapy, whereas the fractions of B and NK cells were elevated. When we evaluated the number of IFN-gamma-secreting cells in relation to the number of present CD4+ T cells, we still found a significant reduction. We conclude that the reduction of IFN-gamma-secreting cells by alemtuzumab is not only due to a reduction of the CD4+ T cell fraction within the peripheral blood mononuclear cell (PBMC) compartment but might also be caused by functional changes or a shift in the distribution of different subtypes in the CD4+ T cell pool.