Single-cell analysis shows that adipose tissue of persons with both HIV and diabetes is enriched for clonal, cytotoxic, and CMV-specific CD4+ T cells

Celestine N Wanjalla; Wyatt J McDonnell; Ramesh Ram; Abha Chopra; Rama Gangula; Shay Leary; Mona Mashayekhi; Joshua D Simmons; Christian M Warren; Samuel Bailin; Curtis L Gabriel; Liang Guo; Briana D Furch; Morgan C Lima; Beverly O Woodward; LaToya Hannah; Mark A Pilkinton; Daniela T Fuller; Kenji Kawai; Renu Virmani; Aloke V Finn; Alyssa H Hasty; Simon A Mallal; Spyros A Kalams; John R Koethe

doi:10.1016/j.xcrm.2021.100205

Single-cell analysis shows that adipose tissue of persons with both HIV and diabetes is enriched for clonal, cytotoxic, and CMV-specific CD4+ T cells

Cell Rep Med. 2021 Feb 16;2(2):100205. doi: 10.1016/j.xcrm.2021.100205.

Authors

Celestine N Wanjalla^{1

2

3}, Wyatt J McDonnell^{1

2

4

5

6}, Ramesh Ram⁷, Abha Chopra⁷, Rama Gangula^{1

3}, Shay Leary⁷, Mona Mashayekhi⁸, Joshua D Simmons^{1

3}, Christian M Warren^{1

3}, Samuel Bailin¹, Curtis L Gabriel⁹, Liang Guo¹⁰, Briana D Furch^{1

3}, Morgan C Lima^{1

3}, Beverly O Woodward^{1

3}, LaToya Hannah⁸, Mark A Pilkinton^{1

2}, Daniela T Fuller¹⁰, Kenji Kawai¹⁰, Renu Virmani¹⁰, Aloke V Finn¹⁰, Alyssa H Hasty^{11

12}, Simon A Mallal^{1

2

5

3

13

7}, Spyros A Kalams^{1

2

5

3}, John R Koethe^{1

2

3

12}

Affiliations

¹ Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
² Center for Translational Immunology and Infectious Disease, Vanderbilt University Medical Center, Nashville, TN, USA.
³ Tennessee Center for AIDS Research, Vanderbilt University Medical Center, Nashville, TN, USA.
⁴ Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA.
⁵ Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN, USA.
⁶ 10x Genomics, Pleasanton, CA, USA.
⁷ Institute for Immunology and Infectious Diseases, Murdoch University, Perth, WA, Australia.
⁸ Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USA.
⁹ Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University, Nashville, TN, USA.
¹⁰ CVPath Institute, Gaithersburg, MD, USA.
¹¹ Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA.
¹² Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, USA.
¹³ VANTAGE, Vanderbilt University Medical Center, Nashville, TN, USA.

Abstract

Persons with HIV are at increased risk for diabetes mellitus compared with individuals without HIV. Adipose tissue is an important regulator of glucose and lipid metabolism, and adipose tissue T cells modulate local inflammatory responses and, by extension, adipocyte function. Persons with HIV and diabetes have a high proportion of CX3CR1⁺ GPR56⁺ CD57⁺ (C-G-C⁺) CD4⁺ T cells in adipose tissue, a subset of which are cytomegalovirus specific, whereas individuals with diabetes but without HIV have predominantly CD69⁺ CD4⁺ T cells. Adipose tissue CD69⁺ and C-G-C⁺ CD4⁺ T cell subsets demonstrate higher receptor clonality compared with the same cells in blood, potentially reflecting antigen-driven expansion, but C-G-C⁺ CD4⁺ T cells have a more inflammatory and cytotoxic RNA transcriptome. Future studies will explore whether viral antigens have a role in recruitment and proliferation of pro-inflammatory C-G-C⁺ CD4⁺ T cells in adipose tissue of persons with HIV.

Keywords: CD4 T cell; CD57; CD69; CX3CR1; GPR56; HIV; adipose tissue; cytomegalovirus; diabetes; single cell.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adipose Tissue / immunology*
CD4-Positive T-Lymphocytes / immunology*
CD8-Positive T-Lymphocytes / immunology
Cytomegalovirus / immunology
Cytomegalovirus Infections / immunology
Diabetes Mellitus / metabolism
HIV Infections / immunology*
Humans
Single-Cell Analysis* / methods
T-Lymphocyte Subsets / immunology

Abstract

Publication types

MeSH terms

Grants and funding