Maturation and Mip-1β Production of Cytomegalovirus-Specific T Cell Responses in Tanzanian Children, Adolescents and Adults: Impact by HIV and Mycobacterium tuberculosis Co-Infections

Damien Portevin; Félicien Moukambi; Maxmillian Mpina; Asli Bauer; Frederick Haraka; Mkunde Chachage; Philipp Metzger; Elmar Saathoff; Petra Clowes; Nyanda E Ntinginya; Andrea Rachow; Michael Hoelscher; Klaus Reither; Claudia A Daubenberger; Christof Geldmacher

doi:10.1371/journal.pone.0126716

Maturation and Mip-1β Production of Cytomegalovirus-Specific T Cell Responses in Tanzanian Children, Adolescents and Adults: Impact by HIV and Mycobacterium tuberculosis Co-Infections

PLoS One. 2015 May 14;10(5):e0126716. doi: 10.1371/journal.pone.0126716. eCollection 2015.

Authors

Affiliations

¹ Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.
² NIMR-Mbeya Medical Research Centre, Mbeya, Tanzania; Department of Infectious Diseases and Tropical Medicine, Medical Centre of the University of Munich, Munich, Germany.
³ Ifakara Health Institute, Bagamoyo, Tanzania.
⁴ NIMR-Mbeya Medical Research Centre, Mbeya, Tanzania.
⁵ Swiss Tropical and Public Health Institute, Basel, Switzerland.
⁶ Department of Infectious Diseases and Tropical Medicine, Medical Centre of the University of Munich, Munich, Germany; German Centre for Infection Research (DZIF), partner site Munich, Munich, Germany.
⁷ Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland; Ifakara Health Institute, Bagamoyo, Tanzania.

Abstract

It is well accepted that aging and HIV infection are associated with quantitative and functional changes of CMV-specific T cell responses. We studied here the expression of Mip-1β and the T cell maturation marker CD27 within CMVpp65-specific CD4(+) and CD8(+) T cells in relation to age, HIV and active Tuberculosis (TB) co-infection in a cohort of Tanzanian volunteers (≤ 16 years of age, n = 108 and ≥ 18 years, n = 79). Independent of HIV co-infection, IFNγ(+) CMVpp65-specific CD4(+) T cell frequencies increased with age. In adults, HIV co-infection further increased the frequencies of these cells. A high capacity for Mip-1β production together with a CD27(low) phenotype was characteristic for these cells in children and adults. Interestingly, in addition to HIV co-infection active TB disease was linked to further down regulation of CD27 and increased capacity of Mip-1β production in CMVpp65-specific CD4+ T cells. These phenotypic and functional changes of CMVpp65-specific CD4 T cells observed during HIV infection and active TB could be associated with increased CMV reactivation rates.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Age Factors
CD4-Positive T-Lymphocytes / immunology*
CD4-Positive T-Lymphocytes / virology
CD8-Positive T-Lymphocytes / immunology*
CD8-Positive T-Lymphocytes / virology
Chemokine CCL4 / metabolism*
Child
Cohort Studies
Coinfection / immunology
Cytomegalovirus / immunology
Cytomegalovirus Infections / complications
Cytomegalovirus Infections / immunology*
Cytomegalovirus Infections / virology
HIV Infections / complications
HIV Infections / diagnosis
HIV Infections / immunology*
Humans
Interferon-gamma / metabolism
Male
Phosphoproteins / metabolism
Risk Factors
Tanzania
Tuberculosis / complications
Tuberculosis / diagnosis
Tuberculosis / immunology*
Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism
Viral Matrix Proteins / metabolism
Young Adult

Substances

Chemokine CCL4
Phosphoproteins
Tumor Necrosis Factor Receptor Superfamily, Member 7
Viral Matrix Proteins
cytomegalovirus matrix protein 65kDa
Interferon-gamma

Grants and funding

The authors gratefully acknowledge funding from the European and Developing Countries Clinical Trials Partnership (EDCTP) for this study as part of the TB CHILD project (IP.2009.32040.007). Co-funding was provided by the German Federal Ministry of Education and Research (BMBF Grant 01KA1006), the Swiss National Science Foundation (32EC30_131192/1) and the German Research Foundation (DFG, grant SA 1878/1-1). Christof Geldmacher`s salary is funded by the German Center for Infection Research (DZIF). Damien Portevin’s salary was funded by the Basel University (Förderung exzellenter junger Forschender). Philipp Metzger was supported by the German Academic Exchange Service (DAAD) with a PROMOS scholarship.