Despite improvement in the prognosis of HIV/AIDS (human immunodeficiency virus/acquired immune deficiency syndrome) patients on antiretroviral therapy (ART), cryptococcal meningitis (CM) still causes 10–15% mortality among HIV-infected patients. The immunological impact of ART on the CD4+ and CD8+ T cell repertoire during cryptococcal co-infection is unclear. We determined longitudinal phenotypic changes in T cell subsets among patients with CM after they initiated ART. We hypothesized that ART alters the clonotypic phenotype and structural composition of CD4+ and CD8+ T cells during CM co-infection. For this substudy, peripheral blood mononuclear cells (PBMC) were isolated at four time points from CM patients following ART initiation during the parent study (ClinicalTrials.gov number, NCT01075152). Phenotypic characterization of CD4+ and CD8+ T cells was done using T cell surface marker monoclonal antibodies by flow cytometry. There was variation in the expression of immunophenotypic markers defining central memory (CD27+CD45R0+), effector memory (CD45R0+CD27–), immune activation (CD38+ and Human Leucocyte Antigen DR (HLA-DR+), and exhaustion (Programmed cell death protein one (PD-1) in the CD4+ T cell subset. In comparison to the CD4+ T cell population, the CD8+ central memory subset declined gradually with minimal increase in the effector memory subset. Both CD4+ and CD8+ T cell immune exhaustion and activation markers remained elevated over 12 weeks. The relative surge and decline in the expression of T cell surface markers outlines a variation in the differentiation of CD4+ T cells during ART treatment during CM co-infection.
Bibliographical noteFunding Information:
Funding: This study was supported by grants from the National Institute of Allergy and Infectious Diseases (NIAID; U01AI089244, K23AI073192, T32AI055433, and K24AI096925), the Wellcome Trust (087540 to Dr. Meya), Alliance for Global Health and Science, Henry Wheeler Centre of Emerging and Neglected Diseases—University of California Berkeley (50288/N7145 to Meya and Alice Bayiyana), and the Fogarty D43 grant to Sam Okurut.
Acknowledgments: We would like to thank the leadership team from the Henry Wheeler Center of Emerging and Neglected Diseases and Alliance for Global Health and Science, University of California, Berkeley for the grant award. We wish to recognize and extend special thanks to Stephen T. Isaacs, Chairman of Aduro BioTech Inc. for funding support. Special acknowledgement to Moses Joloba for mentorship, providing laboratory facilities, administrative support, and opportunities to connect with the funders. We recognize Julia Schaletzky, Jeff Cox, Sarah Stanley, and Zilose Lyons for administrative and scientific support. We thank Nalwadda Geraldine, Ivan Mwebaza, and Emmanuel Nasinghe for the local administrative support.
- Cryptococcal meningitis
- T cell phenotypes