Frequency of Effector Memory Cells Expressing Integrin α4β7 Is Associated With TGF-β1 Levels in Therapy Naïve HIV Infected Women With Low CD4+ T Cell Count.

Nandini J Kasarpalkar,Vainav Patel,Jayanthi Shastri,Lalita Savardekar,Sachee Agrawal,Vikrant M Bhor,Shilpa Bhowmick

doi:10.3389/fimmu.2021.651122

Abstract

Integrin α4β7 expressing CD4+ T cells are preferred targets for HIV infection and are thought to be predictors of disease progression. Concurrent analysis of integrin α4β7 expressing innate and adaptive immune cells was carried out in antiretroviral (ART) therapy naïve HIV infected women in order to determine its contribution to HIV induced immune dysfunction. Our results demonstrate a HIV infection associated decrease in the frequency of integrin α4β7 expressing endocervical T cells along with an increase in the frequency of integrin α4β7 expressing peripheral monocytes and central memory CD4+ T cells, which are considered to be viral reservoirs. We report for the first time an increase in levels of soluble MAdCAM-1 (sMAdCAM-1) in HIV infected individuals as well as an increased frequency and count of integrin CD8+ memory T cells. Correlation analysis indicates that the frequency of effector memory CD8+ T cells expressing integrin α4β7 is associated with levels of both sMAdCAM-1 and TGF-β1. The results of this study also suggest HIV induced alterations in T cell homeostasis to be on account of disparate actions of sMAdCAM-1 and TGF-β1 on integrin α4β7 expressing T cells. The immune correlates identified in this study warrant further investigation to determine their utility in monitoring disease progression.

Highlights

The assault of Human Immunodeficiency virus (HIV) on the immune system is primarily reflected in the decline in absolute count of CD4+ T cells as well as the ratio of CD4/CD8 T cells [1]
Integrin α4β7 is exclusively expressed on immune cells to facilitate gut homing by binding to MAdCAM-1 [48] which is constitutively expressed on endothelial venules of the gut
This notion is affirmed by our observation that a higher frequency of integrin α4β7 expressing cells is found among adaptive immune cells compared to their innate immune counterparts in the systemic circulation

Summary

Introduction

The assault of Human Immunodeficiency virus (HIV) on the immune system is primarily reflected in the decline in absolute count of CD4+ T cells as well as the ratio of CD4/CD8 T cells [1]. Integrin α4β7 in HIV Infected Women cells [8, 9] following HIV infection This dysfunction is attributed to both the direct interaction of immune cells with the viral components as well as altered levels of pro- and antiinflammatory cytokines. Besides these factors, HIV acquisition as well as disease progression depends on the level of expression of HIV co-receptors such as CCR5 [10,11,12] and attachment receptors such as integrin α4β7 [13, 14] on CD4+T cells

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Results

Conclusion