Tobacco smoking increases immune activation and impairs T-cell function in HIV infected patients on antiretrovirals: a cross-sectional pilot study.
BACKGROUND
The influence of tobacco smoking on the immune system of HIV infected individuals is largely unknown. We investigated the impact of tobacco smoking on immune activation, microbial translocation, immune exhaustion and T-cell function in HIV infected individuals.


METHODS
HIV infected smokers and non-smokers (n = 25 each) with documented viral suppression on combination antiretroviral therapy and HIV uninfected smokers and non-smokers (n = 15 each) were enrolled. Markers of immune activation (CD38 and HLA-DR) and immune exhaustion (PD1, Tim3 and CTLA4) were analyzed in peripheral blood mononuclear cells (PBMCs) by flow cytometry. Plasma markers of microbial translocation (soluble-CD14 - sCD14 and lipopolysaccharide - LPS) were measured. Antigen specific functions of CD4+ and CD8+ T-cells were measured, by flow cytometry, in PBMCs after 6 hours stimulation with Cytomegalovirus, Epstein-Barr virus and Influenza Virus (CEF) peptide pool.


RESULTS
Compared to non-smokers, smokers of HIV infected and uninfected groups showed significantly higher CD4+ and CD8+ T-cell activation with increased frequencies of CD38+HLA-DR+ cells with a higher magnitude in HIV infected smokers. Expressions of immune exhaustion markers (PD1, Tim3 and CTLA4) either alone or in combinations were significantly higher in smokers, especially on CD4+ T-cells. Compared to HIV uninfected non-smokers, microbial translocation (sCD14 and LPS) was higher in smokers of both groups and directly correlated with CD4+ and CD8+ T-cell activation. Antigen specific T-cell function showed significantly lower cytokine response of CD4+ and CD8+ T-cells to CEF peptide-pool stimulation in smokers of both HIV infected and uninfected groups.


CONCLUSIONS
Our results suggest that smoking and HIV infection independently influence T-cell immune activation and function and together they present the worst immune profile. Since smoking is widespread among HIV infected individuals, studies are warranted to further evaluate the cumulative effect of smoking on impairment of the immune system and accelerated disease progression.
Department of Pathology, University of Miami-Miller School of Medicine, Miami, Florida, United States of America; Laboratory for Clinical and Biological Studies, University of Miami-Miller School of Medicine, Miami, Florida, United States of America.
Ranjini
R
Valiathan
School of Integrated Science and Humanities, Florida International University, Miami, Florida, United States of America.
Maria J
MJ
Miguez
Laboratory for Clinical and Biological Studies, University of Miami-Miller School of Medicine, Miami, Florida, United States of America.
Bijal
B
Patel
Department of Public Health Sciences, Division of Biostatistics, University of Miami-Miller School of Medicine, Miami, Florida, United States of America.
Kristopher L
KL
Arheart
Department of Pathology, University of Miami-Miller School of Medicine, Miami, Florida, United States of America; Department of Psychiatry and Behavioral Science, University of Miami-Miller School of Medicine, Miami, Florida, United States of America; Laboratory for Clinical and Biological Studies, University of Miami-Miller School of Medicine, Miami, Florida, United States of America.
Deshratn
D
Asthana
D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000378:metabolism; D003430:Cross-Sectional Studies; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D006684:HLA-DR Antigens / Q000378:metabolism; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D010865:Pilot Projects; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects* / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C448908:HAVCR2 protein, human; D006684:HLA-DR Antigens; D000072597:Hepatitis A Virus Cellular Receptor 2; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1