title: Impaired Subset Progression and Polyfunctionality of T Cells in Mice Exposed to Methamphetamine during Chronic LCMV Infection.
abstract: Methamphetamine (METH) is a widely used psychostimulant that severely impacts the host's innate and adaptive immune systems and has profound immunological implications. T cells play a critical role in orchestrating immune responses. We have shown recently how chronic exposure to METH affects T cell activation using a murine model of lymphocytic choriomeningitis virus (LCMV) infection. Using the TriCOM (trinary state combinations) feature of GemStone™ to study the polyfunctionality of T cells, we have analyzed how METH affected the cytokine production pattern over the course of chronic LCMV infection. Furthermore, we have studied in detail the effects of METH on splenic T cell functions, such as cytokine production and degranulation, and how they regulate each other. We used the Probability State Modeling (PSM) program to visualize the differentiation of effector/memory T cell subsets during LCMV infection and analyze the effects of METH on T cell subset progression. We recently demonstrated that METH increased PD-1 expression on T cells during viral infection. In this study, we further analyzed the impact of PD-1 expression on T cell functional markers as well as its expression in the effector/memory subsets. Overall, our study indicates that analyzing polyfunctionality of T cells can provide additional insight into T cell effector functions. Analysis of T cell heterogeneity is important to highlight changes in the evolution of memory/effector functions during chronic viral infections. Our study also highlights the impact of METH on PD-1 expression and its consequences on T cell responses.
authors.affiliation: Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, United States of America.
authors.forename: Uma
authors.initials: U
authors.lastname: Sriram
authors.affiliation: Verity Software House, Topsham, Maine, United States of America.
authors.forename: Beth L
authors.initials: BL
authors.lastname: Hill
authors.affiliation: Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, United States of America.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Cenna
authors.affiliation: Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, United States of America.
authors.forename: Larisa
authors.initials: L
authors.lastname: Gofman
authors.affiliation: Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, United States of America.
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Fernandes
authors.affiliation: Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, United States of America.
authors.forename: Bijayesh
authors.initials: B
authors.lastname: Haldar
authors.affiliation: Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, United States of America.|Center for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United States of America.
authors.forename: Raghava
authors.initials: R
authors.lastname: Potula
mesh_terms: D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000697:Central Nervous System Stimulants; D016207:Cytokines; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D008694:Methamphetamine