Early transcriptional and epigenetic divergence of CD8+ T cells responding to acute versus chronic infection.

During a microbial infection, responding CD8+ T cells give rise to effector cells that provide acute host defense and memory cells that provide sustained protection. An alternative outcome is exhaustion, a state of T cell dysfunction that occurs in the context of chronic infections and cancer. Although it is evident that exhausted CD8+ T (TEX) cells are phenotypically and molecularly distinct from effector and memory CD8+ T cells, the factors regulating the earliest events in the differentiation process of TEX cells remain incompletely understood. Here, we performed single-cell RNA-sequencing and single-cell ATAC-sequencing of CD8+ T cells responding to LCMV-Armstrong (LCMV-Arm) or LCMV-Clone 13 (LCMV-Cl13), which result in acute or chronic infections, respectively. Compared to CD8+ T cells that had undergone their first division in response to LCMV-Arm (Div1ARM) cells, CD8+ T cells that had undergone their first division in response to LCMV-Cl13 (Div1CL13) expressed higher levels of genes encoding transcription factors previously associated with exhaustion, along with higher levels of Ezh2, the catalytic component of the Polycomb Repressive Complex 2 (PRC2) complex, which mediates epigenetic silencing. Modulation of Ezh2 resulted in altered expression of exhaustion-associated molecules by CD8+ T cells responding to LCMV-Cl13, though the specific cellular and infectious contexts, rather than simply the level of Ezh2 expression, likely determine the eventual outcome. Taken together, these findings suggest that the differentiation paths of CD8+ T cells responding to acute versus chronic infections may diverge earlier than previously appreciated.

Assessing Hepatitis B Knowledge Among Native Hawaiians and Pacific Islanders in San Diego.

BACKGROUND: Asian-Americans and Pacific Islanders comprise 6% of the U.S. population, but 50% of chronic hepatitis B cases and have a cancer mortality that is 60% higher than non-Hispanic Whites. The objective of this study was to assess knowledge of HBV transmission, symptoms/sequelae and treatment among NHPIs in San Diego. METHODS: Self-administered surveys were distributed using convenience sampling at the 24th Annual Pacific Islander Festival in San Diego in 2018. RESULTS: Overall knowledge scores were low (mean: 9.8 out of 28) among participants. Compared to U.S.- born (mean: 11.6), participants born in Pacific Island countries and territories (mean: 8.5) had lower knowledge scores (p = 0.017) and lower self-reported vaccination rates (50% vaccinated vs 27%, respectively, p = 0.025). DISCUSSION: Lack of HBV knowledge, low vaccination rates and the discordance between knowledge and behavior regarding HBV vaccination elicits an urgent need to collaborate with NHPI communities for HBV education, screening, immunization and treatment.