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; La Toya 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

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, La Toya Hannah, Mark A. Pilkinton, Daniela T. Fuller, Kenji Kawai, Renu VirmaniAloke V. Finn, Alyssa H. Hasty, Simon A. Mallal, Spyros A. Kalams, John R. Koethe

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

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.

Original language	English (US)
Article number	100205
Journal	Cell Reports Medicine
Volume	2
Issue number	2
DOIs	https://doi.org/10.1016/j.xcrm.2021.100205
State	Published - Feb 16 2021
Externally published	Yes

Keywords

adipose tissue
CD4 T cell
CD57
CD69
CX3CR1
cytomegalovirus
diabetes
GPR56
HIV
single cell

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.xcrm.2021.100205

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Wanjalla, C. N., McDonnell, W. J., Ram, R., Chopra, A., Gangula, R., Leary, S., Mashayekhi, M., Simmons, J. D., Warren, C. M., Bailin, S., Gabriel, C. L., Guo, L., Furch, B. D., Lima, M. C., Woodward, B. O., Hannah, L. T., Pilkinton, M. A., Fuller, D. T., Kawai, K., ... Koethe, J. R. (2021). 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 Reports Medicine, 2(2), Article 100205. https://doi.org/10.1016/j.xcrm.2021.100205

Wanjalla, CN, McDonnell, WJ, Ram, R, Chopra, A, Gangula, R, Leary, S, Mashayekhi, M, Simmons, JD, Warren, CM, Bailin, S, Gabriel, CL, Guo, L, Furch, BD, Lima, MC, Woodward, BO, Hannah, LT, Pilkinton, MA, Fuller, DT, Kawai, K, Virmani, R, Finn, AV, Hasty, AH, Mallal, SA, Kalams, SA & Koethe, JR 2021, '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 Reports Medicine, vol. 2, no. 2, 100205. https://doi.org/10.1016/j.xcrm.2021.100205

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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 = "adipose tissue, CD4 T cell, CD57, CD69, CX3CR1, cytomegalovirus, diabetes, GPR56, HIV, single cell",

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AU - Wanjalla, Celestine N.

AU - McDonnell, Wyatt J.

AU - Ram, Ramesh

AU - Chopra, Abha

AU - Gangula, Rama

AU - Leary, Shay

AU - Mashayekhi, Mona

AU - Simmons, Joshua D.

AU - Warren, Christian M.

AU - Bailin, Samuel

AU - Gabriel, Curtis L.

AU - Guo, Liang

AU - Furch, Briana D.

AU - Lima, Morgan C.

AU - Woodward, Beverly O.

AU - Hannah, La Toya

AU - Pilkinton, Mark A.

AU - Fuller, Daniela T.

AU - Kawai, Kenji

AU - Virmani, Renu

AU - Finn, Aloke V.

AU - Hasty, Alyssa H.

AU - Mallal, Simon A.

AU - Kalams, Spyros A.

AU - Koethe, John R.

PY - 2021/2/16

Y1 - 2021/2/16

N2 - 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.

AB - 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.

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KW - CD4 T cell

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KW - single cell

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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