Comparison of the integrin α4β7 expression pattern of memory T cell subsets in HIV infection and ulcerative colitis

Abstract

Anti-α4β7 therapy with vedolizumab (VDZ) has been suggested as possible immune intervention in HIV. Relatively little is known about the α4β7-integrin (α4β7) expression of different T-cell subsets in different anatomical compartments of healthy individuals, patients with HIV or inflammatory bowel disease (IBD). Surface expression of α4β7 as well as the frequency of activation, homing and exhaustion markers of T cells were assessed by multicolour flow cytometry in healthy volunteers (n = 15) compared to HIV infected patients (n = 52) or patients diagnosed with ulcerative colitis (UC) (n = 14), 6 of whom treated with vedolizumab. In addition, lymph nodal cells (n = 6), gut-derived cells of healthy volunteers (n = 5) and patients with UC (n = 6) were analysed. Additionally, we studied longitudinal PBMC samples of an HIV patient who was treated with vedolizumab for concomitant UC. Overall, only minor variations of the frequency of α4β7 on total CD4 + T cells were detectable regardless of the disease status or (VDZ) treatment status in peripheral blood and the studied tissues. Peripheral α4β7 + CD4 + T cells of healthy individuals and patients with UC showed a higher activation status and were more frequently CCR5 + than their α4β7 - counterparts. Also, the frequency of α4β7 + cells was significantly lower in peripheral blood CD4 + effector memory T cells of HIV-infected compared to healthy individuals and this reduced frequency did not recover in HIV patients on ART. Conversely, the frequency of peripheral blood naïve α4β7 + CD4 + T cells was significantly reduced under VDZ treatment. The results of the current study will contribute to the understanding of the dynamics of α4β7 expression pattern on T cells in HIV and UC and will be useful for future studies investigating VDZ as possible HIV cure strategy.

Analysis of Co-inhibitory Receptor Expression in COVID-19 Infection Compared to Acute Plasmodium falciparum Malaria: LAG-3 and TIM-3 Correlate With T Cell Activation and Course of Disease

“…Based on the established differentiation markers CCR7, CD45RO, and CD27 ( 39 ), we defined naïve (CCR7 + CD45RO − ), central memory CM (CCR7 + CD45RO + ), transitional memory TM (CCR7 − CD45RO + CD27 + ), effector memory EM (CCR7 − CD45RO + CD27 − ) and terminal effector memory EMRA (CCR7 − CD45RO − ) CD8 + and CD4 + T cells and assessed the frequency of the activation markers on each subset ( 39 ). Overall, we saw an increase of CD8 + EM T cells and CD8 + and CD4 + CM T cells in both COVID-19 and malaria compared to healthy individuals ( Figure 1C ).…”

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

“…Recent evidence suggests the formation of latent HIV reservoirs through differentiation of HIV infected integrin α 4 β 7 expressing effector memory T cells into central memory cells in vitro under the influence of transforming growth factor β (TGF-β) (26). Integrin α 4 β 7 -HIV gp120 interaction has also been targeted using monoclonal antibodies for prophylactic as well as therapeutic applications in both animal models (27)(28)(29)(30) and human studies (31).…”

“…The frequency of integrin α 4 β 7 expressing cells varies among T cells subsets ( 32 ) as well as other immune cells in healthy and diseased states ( 31 , 33 , 34 ). Moreover, interaction of HIV gp120 with integrin α 4 β 7 on different immune cells also hampers their function ( 35 – 37 ).…”

Decreased Frequency of Intestinal CD39+ γδ+ T Cells With Tissue-Resident Memory Phenotype in Inflammatory Bowel Disease

“…Collected in sterile PBS, the samples were processed as previously described ( 27 , 28 ). In brief, after incubation in Hank’s Balanced Salt Solution (HBSS) containing DTT and EDTA for a short digestion period, they were stored in 6-well, low-binding plates overnight in RPMI supplemented with 10 % FCS, antibiotics and antifungals (1 mg/mL Piperacillin/Tazobactam and 1.25 μg/mL Amphotericin B).…”