Toll-Like Receptor Ligands Induce Human T Cell Activation and Death, a Model for HIV Pathogenesis

Background: Recently, heightened systemic translocation of microbial products was found in persons with chronic HIV infection and this was linked to immune activation and CD4 + T cell homeostasis. Methodology: We examined here the effects of microbial Toll-like receptor (TLR) ligands on T cell activation in vitro. Conclusions/Findings: We show that exposure to TLR ligands results in activation of memory and effector CD4 + and CD8 + T cells. After exposure to each of 8 different ligands that activate TLRs 2, 3, 4, 5, 7, 8, and 9, CD8 + T cells are activated and gain expression of the C type lectin CD69 that may promote their retention in lymphoid tissues. In contrast, CD4 + T cells rarely increase CD69 expression but instead enter cell cycle. Despite activation and cell cycle entry, CD4 + T cells divide poorly and instead, disproportionately undergo activation-induced cell death. Systemic exposure to TLR agonists may therefore increase immune activation, effector cell sequestration in lymphoid tissues and T cell turnover. These events may contribute to the pathogenesis of immune dysfunction and CD4+ T cell losses in chronic infection with the human immunodeficiency virus

The most primitive CM chondrites, Asuka 12085, 12169, and 12236, of subtypes 3.0–2.8: Their characteristic features and classification

CM chondrites (CMs) are the most abundant group of carbonaceous chondrites. CMs experienced varying degrees of secondary aqueous alteration and heating that modified or destroyed their primitive features. We have studied three chondrites, Asuka (A) 12085, A 12169, and A 12236. Their modal compositions, chondrule size distributions, and bulk composition indicate that they are CMs. However, the common occurrence of melilite in CAIs and glass in chondrules, abundant Fe–Ni metal, the absence of tochilinite-cronstedtite intergrowths, and almost no phyllosilicates, all suggest that these chondrites, especially A 12169, experienced only minimal aqueous alteration. The textures and compositions of metal and sulfides, the lack of ferroan rims on AOA olivines, the compositional distribution of ferroan olivine, and the Raman spectra of their matrices, indicate that these chondrites experienced neither significant heating nor dehydration. These chondrites, especially A 12169, are the most primitive CMs so far reported. The degree of the alteration increases from A 12169, through A 12236, to A 12085. We propose the criteria for subtypes of 3.0–2.8 for CMs. A 12169, A 12236, and A 12085 are classified as subtype 3.0, 2.9, and 2.8, respectively. The oxygen isotopic composition of the Asuka CMs is consistent with these samples having experienced only a limited degree of aqueous alteration. The CM and CO groups are probably not derived from a single heterogeneous parent body. These chondrites are also of particular significance in view of the imminent return of sample material from the asteroids Ryugu and Bennu