Impaired Subset Progression and Polyfunctionality of T Cells in Mice Exposed to Methamphetamine during Chronic LCMV Infection

• Published in: PloS one Vol. 11; no. 10; p. e0164966
• Main Authors: Sriram, Uma, Hill, Beth L, Cenna, Jonathan M, Gofman, Larisa, Fernandes, Nicole C, Haldar, Bijayesh, Potula, Raghava
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19.10.2016; Public Library of Science (PLoS)
• Subjects: Adaptive systems; Analysis; Animal models; Animals; Arenaviridae; Biology and Life Sciences; Cell activation; Central Nervous System Stimulants - administration & dosage; Central Nervous System Stimulants - pharmacology; Chronic exposure; Chronic infection; Cytokines; Cytokines - metabolism; Cytotoxicity; Degranulation; Disease Models, Animal; Drug dosages; Gene Expression Regulation - drug effects; Health aspects; HIV; Human immunodeficiency virus; Immune response; Immune system; Immunoglobulins; Immunological memory; Immunology; Impact analysis; Infection; Infections; Laboratory animals; Lymphocyte Activation - drug effects; Lymphocytes; Lymphocytes T; Lymphocytic Choriomeningitis - immunology; Lymphocytic choriomeningitis virus; Male; Mathematical models; Medical research; Medicine; Medicine and Health Sciences; Memory cells; Methamphetamine; Methamphetamine - adverse effects; Methamphetamine - pharmacology; Mice; Mice, Inbred C57BL; Pathology; PD-1 protein; Programmed Cell Death 1 Receptor - metabolism; Spleen; Spleen - drug effects; Spleen - immunology; Studies; Substance abuse treatment; T cell receptors; T cells; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - metabolism; Up-Regulation; Viral infections; Virology; Viruses; United States > US; Maine
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0164966

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.