Characterization of T Follicular Helper Cells and T Follicular Regulatory Cells in HIV-Infected and Sero-Negative Individuals

Bradley Salvatore; Rachel S Resop; Brent R Gordon; Marta Epeldegui; Otoniel Martinez-Maza; Begoña Comin-Anduix; Alex Lam; Ting-Ting Wu; Christel H Uittenbogaart

doi:10.3390/cells12020296

Characterization of T Follicular Helper Cells and T Follicular Regulatory Cells in HIV-Infected and Sero-Negative Individuals

Cells. 2023 Jan 12;12(2):296. doi: 10.3390/cells12020296.

Authors

Bradley Salvatore¹, Rachel S Resop^{1

2}, Brent R Gordon^{1

2}, Marta Epeldegui^{2

3

4}, Otoniel Martinez-Maza^{2

3

4}, Begoña Comin-Anduix^{4

5}, Alex Lam⁶, Ting-Ting Wu^{2

4

6}, Christel H Uittenbogaart^{1

2

4

7}

Affiliations

¹ Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA.
² UCLA AIDS Institute, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA.
³ Department of Obstetrics and Gynecology, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA.
⁴ Jonsson Comprehensive Cancer Center (JCCC), University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA.
⁵ Department of Surgical-Oncology, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA.
⁶ Department of Molecular Pharmacology, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA.
⁷ Department of Pediatrics, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA.

Abstract

Humoral immune response is important in fighting pathogens by the production of specific antibodies by B cells. In germinal centers, T follicular helper (TFH) cells provide important help to B-cell antibody production but also contribute to HIV persistence. T follicular regulatory (TFR) cells, which inhibit the function of TFH cells, express similar surface markers. Since FOXP3 is the only marker that distinguishes TFR from TFH cells it is unknown whether the increase in TFH cells observed in HIV infection and HIV persistence may be partly due to an increase in TFR cells. Using multicolor flow cytometry to detect TFH and TFR cells in cryopreserved peripheral blood mononuclear cells from HIV-infected and non-infected participants in the UCLA Multicenter AIDS Cohort Study (MACS), we identified CD3⁺CXCR5⁺CD4⁺CD8^-BCL6⁺ peripheral blood TFH (pTFH) cells and CD3⁺CXCR5⁺CD4⁺CD8^-FOXP3⁺ peripheral blood TFR (pTFR) cells. Unlike TFR cells in germinal centers, pTFR cells do not express B cell lymphoma 6 (BCL6), a TFH cell master transcriptional regulator. Our major findings are that the frequency of pTFH cells, but not pTFR cells was higher in HIV-infected participants of the MACS and that pTFH cells expressed less CCR5 in HIV-infected MACS participants. Constitutive expression of CCR5 in TFR cells supports their potential to contribute to HIV persistence.

Keywords: HIV; T follicular helper cells; T follicular regulatory cells; flow cytometry.

Publication types

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

MeSH terms

Acquired Immunodeficiency Syndrome* / metabolism
Cohort Studies
Forkhead Transcription Factors / metabolism
HIV Infections* / metabolism
Humans
Leukocytes, Mononuclear / metabolism
T Follicular Helper Cells / metabolism
T-Lymphocytes, Helper-Inducer

Substances

Forkhead Transcription Factors

Grants and funding

U01 HL146333/HL/NHLBI NIH HHS/United States