CD4+T cells in ageing-associated interstitial lung abnormalities show evidence of pro-inflammatory phenotypic and functional profile

BackgroundInterstitial lung abnormalities (ILA) occur in around 10% of subjects over 60 years, and are associated with a higher rate of all-cause mortality. The pathogenic mechanisms are unclear, and the putative contribution of alterations in the immune response has not been explored. Normal ageing is associated with immune deficiencies, including Naïve T-cell decrease and greater expression of the proliferative-limiting, co-inhibitory receptor killer-cell lectin-like receptor G1 (KLRG1).ObjectiveTo evaluate the frequency and activation state of different T-cell subpopulations in ILA subjects.MethodsPeripheral blood mononuclear cells were obtained from 15 individuals with ILA, 21 age-matched controls and 28 healthy young subjects. T-cells phenotype was characterised by flow cytometry, and proliferation and activation by stimulation with anti-CD3/anti-CD28 or phorbol myristate acetate/ionomycin; KLRG1 isoforms were evaluated by western blot and cytokines were quantified by ELISA and Multiplex.ResultsA significant increase of Naïve CD4+T cells together with a decrease of central and effector memory CD4+T cells was observed in ILA compared with age-matched controls. CD4+T cells from ILA subjects exhibited greater basal proliferation, which raised after anti-CD3/anti-CD28 stimulation. Additionally, a significant increase in the levels of interleukin-6 and interferon gamma was observed in isolated CD4+T cells and plasma of ILA subjects. They also displayed fewer KLRG1+/CD4+T cells with an increase of circulating E-cadherin, the ligand of KLRG1+. No changes were observed with CD8+T cell subsets.ConclusionCD4+T cells from ILA subjects are highly proliferative and show an excessive functional activity, likely related to the loss of KLRG1 expression, which may contribute to an inflammatory state and the development of ILA.

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Individual Immune-Modulatory Capabilities of MSC-Derived Extracellular Vesicle (EV) Preparations and Recipient-Dependent Responsiveness

International Journal of Molecular Sciences ◽

10.3390/ijms20071642 ◽

2019 ◽

Vol 20 (7) ◽

pp. 1642 ◽

Cited By ~ 13

Author(s):

Lambros Kordelas ◽

Esther Schwich ◽

Robin Dittrich ◽

Peter Horn ◽

Dietrich Beelen ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Mononuclear Cells ◽

Therapeutic Option ◽

T Cell Response ◽

Cytokine Profile ◽

T Cell Subsets ◽

Effector Memory ◽

Peripheral Blood Mononuclear ◽

Vitro Assay

Treatment with extracellular vesicles (EVs) derived from mesenchymal stem/stromal cells (MSCs) have been suggested as novel therapeutic option in acute inflammation-associated disorders due to their immune-modulatory capacities. As we have previously observed differences in the cytokine profile of independent MSC-EV preparations, functional differences of MSC-EV preparations have to be considered. To evaluate the immune-modulatory capabilities of specific MSC-EV preparations, reliable assays are required to characterize the functionality of MSC-EV preparations prior to administration to a patient. To this end, we established an in vitro assay evaluating the immune-modulatory capacities of MSC-EV preparations. Here, we compared the efficacy of four independent MSC-EV preparations to modulate the induction of T cell differentiation and cytokine production after phorbol 12-myristate 13-acetate (PMA)/Ionomycin stimulation of peripheral blood mononuclear cells (PBMC) derived from six healthy donors. Flow cytometric analyses revealed that the four MSC-EV preparations differentially modulate the expression of surface markers, such as CD45RA, on CD4+ and CD8+ T cells, resulting in shifts in the frequencies of effector and effector memory T cells. Moreover, cytokine profile in T cell subsets was affected in a MSC-EV-specific manner exclusively in CD8+ naïve T cells. Strikingly, hierarchical clustering revealed that the T cell response towards the MSC-EV preparations largely varied among the different PBMC donors. Thus, besides defining functional activity of MSC-EV preparations, it will be crucial to test whether patients intended for treatment with MSC-EV preparations are in principal competent to respond to the envisioned MSC-EV therapy.

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CD4+ T cells are essential for the development of destructive thyroiditis induced by anti–PD-1 antibody in thyroglobulin-immunized mice

Science Translational Medicine ◽

10.1126/scitranslmed.abb7495 ◽

2021 ◽

Vol 13 (593) ◽

pp. eabb7495

Author(s):

Yoshinori Yasuda ◽

Shintaro Iwama ◽

Daisuke Sugiyama ◽

Takayuki Okuji ◽

Tomoko Kobayashi ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Lymph Nodes ◽

Mononuclear Cells ◽

Critical Role ◽

T Cell Subsets ◽

Effector Memory ◽

Histopathological Analysis ◽

Activated T Cells ◽

Cervical Lymph Nodes

Immune-related adverse events induced by anti–programmed cell death–1 antibodies (PD-1-Ab), including destructive thyroiditis (thyroid-irAE), are thought to be caused by activated T cells. However, the T cell subsets that are directly responsible for damaging self-organs remain unclear. To clarify which T cell subsets are involved in the development of thyroid-irAE, a mouse model of thyroid-irAE was analyzed. PD-1-Ab administration 2.5 months after immunization with thyroglobulin caused destructive thyroiditis. Thyroiditis was completely prevented by previous depletion of CD4+ T cells and partially prevented by depleting CD8+ T cells. The frequencies of central and effector memory CD4+ T cell subsets and the secretion of interferon-γ after stimulation with thyroglobulin were increased in the cervical lymph nodes of mice with thyroid-irAE compared with controls. Histopathological analysis revealed infiltration of CD4+ T cells expressing granzyme B in thyroid glands and major histocompatibility complex class II expression on thyrocytes in mice with thyroid-irAE. Adoptive transfer of CD4+ T cells from cervical lymph nodes in mice with thyroid-irAE caused destruction of thyroid follicular architecture in the irradiated recipient mice. Flow cytometric analyses showed that the frequencies of central and effector memory CD4+ T cells expressing the cytotoxic marker CD27 were higher in peripheral blood mononuclear cells collected from patients with thyroid-irAE induced by PD-1-Ab versus those without. These data suggest a critical role for cytotoxic memory CD4+ T cells activated by PD-1-Ab in the pathogenesis of thyroid-irAE.

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Expression Cloning of an Immunodominant Family of Mycobacterium tuberculosis Antigens Using Human Cd4+ T Cells

Journal of Experimental Medicine ◽

10.1084/jem.191.3.551 ◽

2000 ◽

Vol 191 (3) ◽

pp. 551-560 ◽

Cited By ~ 88

Author(s):

Mark R. Alderson ◽

Teresa Bement ◽

Craig H. Day ◽

Liqing Zhu ◽

David Molesh ◽

...

Keyword(s):

T Cells ◽

Mycobacterium Tuberculosis ◽

T Cell ◽

Cd4 T Cells ◽

Mononuclear Cells ◽

Genomic Library ◽

Cell Epitope ◽

Single Amino Acid ◽

Expression Cloning ◽

Peripheral Blood Mononuclear

Development of a subunit vaccine for Mycobacterium tuberculosis (Mtb) is likely to be dependent on the identification of T cell antigens that induce strong proliferation and interferon γ production from healthy purified protein derivative (PPD)+ donors. We have developed a sensitive and rapid technique for screening an Mtb genomic library expressed in Escherichia coli using Mtb-specific CD4+ T cells. Using this technique, we identified a family of highly related Mtb antigens. The gene of one family member encodes a 9.9-kD antigen, termed Mtb9.9A. Recombinant Mtb9.9A protein, expressed and purified from E. coli, elicited strong T cell proliferation and IFN-γ production by peripheral blood mononuclear cells from PPD+ but not PPD− individuals. Southern blot analysis and examination of the Mtb genome sequence revealed a family of highly related genes. A T cell line from a PPD+ donor that failed to react with recombinant Mtb9.9A recognized one of the other family members, Mtb9.9C. Synthetic peptides were used to map the T cell epitope recognized by this line, and revealed a single amino acid substitution in this region when compared with Mtb9.9A. The direct identification of antigens using T cells from immune donors will undoubtedly be critical for the development of vaccines to several intracellular pathogens.

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Donor-Derived CD4+ T Cells and Human Herpesvirus 6B Detection After Allogeneic Hematopoietic Cell Transplantation

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa422 ◽

2020 ◽

Author(s):

Derek J Hanson ◽

Hu Xie ◽

Danielle M Zerr ◽

Wendy M Leisenring ◽

Keith R Jerome ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Cell Transplantation ◽

Cd4 T Cells ◽

Hematopoietic Cell Transplantation ◽

Mononuclear Cells ◽

Human Herpesvirus ◽

Hematopoietic Cell ◽

Allogeneic Hematopoietic Cell Transplantation ◽

Peripheral Blood Mononuclear

Abstract We sought to determine whether donor-derived human herpesvirus (HHV) 6B–specific CD4+ T-cell abundance is correlated with HHV-6B detection after allogeneic hematopoietic cell transplantation. We identified 33 patients who received HLA-matched, non–T-cell–depleted, myeloablative allogeneic hematopoietic cell transplantation and underwent weekly plasma polymerase chain reaction testing for HHV-6B for 100 days thereafter. We tested donor peripheral blood mononuclear cells for HHV-6B–specific CD4+ T cells. Patients with HHV-6B detection above the median peak viral load (200 copies/mL) received approximately 10-fold fewer donor-derived total or HHV-6B–specific CD4+ T cells than those with peak HHV-6B detection at ≤200 copies/mL or with no HHV-6B detection. These data suggest the importance of donor-derived immunity for controlling HHV-6B reactivation.

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Ex Vivo Fludarabine Selectively Depletes Human Naive T-Cell Subsets: A Step Toward Modifying Donor Lymphocyte Infusion.

Blood ◽

10.1182/blood.v106.11.1071.1071 ◽

2005 ◽

Vol 106 (11) ◽

pp. 1071-1071

Author(s):

Melody M. Smith ◽

Cynthia R. Giver ◽

Edmund K. Waller ◽

Christopher R. Flowers

Keyword(s):

T Cells ◽

T Cell ◽

Cd8 T Cells ◽

Cd4 T Cells ◽

Memory T Cells ◽

Ex Vivo ◽

T Cell Subsets ◽

Effector Memory ◽

Naïve T Cell ◽

Naive T Cell

Abstract Ex vivo modification of donor lymphocytes with purine analogs (mDL) may help to minimize graft versus host disease (GvHD) while providing beneficial graft versus leukemia (GvL) effects. In a murine model system, we have shown that allogeneic donor splenocytes, treated with fludarabine ex vivo have significantly reduced GvHD activity when transferred to irradiated recipient mice, and retain anti-viral and GvL activities (Giver, 2003). This effect appears to be mediated by relative depletion of donor CD4 CD44low, “naive” T-cells. As a first step toward developing mDL for use in patients, we sought to evaluate the effects of ex vivo fludarabine exposure on human T-cell subsets, and to determine the minimum dose of fludarabine required to achieve this effect. Methods: Peripheral blood mononuclear cell samples from 6 healthy volunteers were evaluated at 0, 24, 48, and 72 hour time points after ex vivo incubation in varying dosages of fludarabine: 2, 5, and 10(n=3) mcg/ml. Fludarabine incubated samples were compared to samples that received no fludarabine (untreated). The total viable cell number was determined and the fractions and absolute numbers of viable CD4 and CD8 naïve and memory T-cells were determined using flow cytometry after incubation with 7-AAD (dead cell stain), CD4, CD8, CD45RA, CD62L, and CCR7 antibodies, and measuring the total viable cells/ml. Results: The numbers of viable CD4 and CD8 T-cells remained relatively stable in control cultures. Without fludarabine, the average viability at 72 hr of naive and memory T-cells were 92% and 77% for CD4 and 86% and 63% for CD 8 (Fig. 1A). Naive CD4 T-cells were more sensitive to fludarabine-induced death than memory CD4 cells. At 72 hr, the average viability of fludarabine-treated naive CD4 T-cells was 33% at 2 mcg/ml (8.2X the reduction observed in untreated cells) and 30% at 5 mcg/ml, while memory CD4 T-cells averaged 47% viability at 2 mcg/ml (2.3X the reduction observed in untreated cells) (Fig. 1B) and 38% at 5 mcg/ml. The average viability of naive CD8 T-cells at 72 hr was 27% at 2 mcg/ml and 20% at 5 mcg/ml, while memory CD8 T-cell viability was 22% at 2 mcg/ml and 17% at 5 mcg/ml. Analyses on central memory, effector memory, and Temra T-cells, and B-cell and dendritic cell subsets are ongoing. The 5 and 10 mcg/ml doses also yielded similar results in 3 initial subjects, suggesting that 2 mcg/ml or a lower dose of fludarabine is sufficient to achieve relative depletion of the naive T-cell subset. Conclusions: Future work will determine the minimal dose of fludarabine to achieve this effect, test the feasibility of using ex vivo nucleoside analog incubation to reduce alloreactivity in samples from patient/donor pairs, and determine the maximum tolerated dose of mDL in a phase 1 clinical trial with patients at high risk for relapse and infectious complications following allogeneic transplantation. Figure Figure

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CD70 Expression on HTLV-1 Infected T Cells of Carriers and ATL Patients and Its Clinical Significance

Blood ◽

10.1182/blood.v116.21.1730.1730 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1730-1730

Author(s):

Izumi Masamoto ◽

Sawako Horai ◽

Tomohiro Kozako ◽

Makoto Yoshimitsu ◽

Junko Niimoto ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Cd4 T Cells ◽

Mononuclear Cells ◽

Conflicts Of Interest ◽

Surveillance Systems ◽

Peripheral Blood Mononuclear ◽

Tax Protein ◽

Infected Cells

Abstract Abstract 1730 Human T-lymphotropic virus type-1(HTLV-1) is the causative agent of adult T cell leukemia/lymphoma (ATL). HTLV-1 infected T cell growth or leukemogenesis in ATL is controlled by various host immune surveillance systems. Among them, CD70 on HTLV-1 infected T cells coupled with CD27 on virus specific cytotoxic T cells has been suggested to play an important role in ATL leukemogenesis. The CD70 molecule is the only known ligand for CD27, a member of the tumor necrosis factor (TNF) receptor superfamily 7. This negative immunoregulatory pathway downregulates cytotoxic T lymphocyte activity against CD70-expressing virus infected cells. In the present study, we examined CD70 expression on primary lymphocytes of HTLV-1 carriers and ATL patients, its relationship with HTLV-1 Tax protein expression, and the effect on CTL induction. CD70 expression was higher on peripheral blood mononuclear cells (PBMCs) of HTLV-1 infected carriers compared with healthy donors (p = 0.021, n = 21, Mann-Whitney U test), and higher in ATL patients compared to carriers (p = 0.045, n = 38, Mann-Whitney U test). CD70 expression may be observed in CD4 T cells, as well as B cells, but not in CD8 T cells or monocytes. CD70 expression in CD4 T cells is related to HTLV-1 infection, because of increased detection of HTLV-1 Tax protein during over night culture of CD70-expressing cells. Experiments using an ATL cell line, in which Tax expression is inducible by doxycycline stimulation, demonstrated enhanced CD70 expression when Tax protein was induced in HTLV-1 infected cells. Anti-CD70 antibody enhanced CD107a mobilization, a marker of recent cytotoxic degranulation, in HTLV-1 Tax specific CTLs in PBMCs from asymptomatic carriers in vitro, suggesting that the CD70/CD27 pathway plays an important role in the immune response to HTLV-1 infection in carriers, as well as ATL patients. Disclosures: No relevant conflicts of interest to declare.

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Interplay between IL-10, IFN-γ, IL-17A and PD-1 Expressing EBNA1-Specific CD4+ and CD8+ T Cell Responses in the Etiologic Pathway to Endemic Burkitt Lymphoma

Cancers ◽

10.3390/cancers13215375 ◽

2021 ◽

Vol 13 (21) ◽

pp. 5375

Author(s):

Catherine S. Forconi ◽

David H. Mulama ◽

Priya Saikumar Lakshmi ◽

Joslyn Foley ◽

Juliana A. Otieno ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Burkitt Lymphoma ◽

Cd4 T Cells ◽

Cd8 T Cell ◽

T Cell Response ◽

T Cell Subsets ◽

Effector Memory ◽

Healthy Children ◽

Ifn Γ

Children diagnosed with endemic Burkitt lymphoma (eBL) are deficient in interferon-γ (IFN-γ) responses to Epstein–Barr Nuclear Antigen1 (EBNA1), the viral protein that defines the latency I pattern in this B cell tumor. However, the contributions of immune-regulatory cytokines and phenotypes of the EBNA1-specific T cells have not been characterized for eBL. Using a bespoke flow cytometry assay we measured intracellular IFN-γ, IL-10, IL-17A expression and phenotyped CD4+ and CD8+ T cell effector memory subsets specific to EBNA1 for eBL patients compared to two groups of healthy children with divergent malaria exposures. In response to EBNA1 and a malaria antigen (PfSEA-1A), the three study groups exhibited strikingly different cytokine expression and T cell memory profiles. EBNA1-specific IFN-γ-producing CD4+ T cell response rates were lowest in eBL (40%) compared to children with high malaria (84%) and low malaria (66%) exposures (p < 0.0001 and p = 0.0004, respectively). However, eBL patients did not differ in CD8+ T cell response rates or the magnitude of IFN-γ expression. In contrast, eBL children were more likely to have EBNA1-specific CD4+ T cells expressing IL-10, and less likely to have polyfunctional IFN-γ+IL-10+ CD4+ T cells (p = 0.02). They were also more likely to have IFN-γ+IL-17A+, IFN-γ+ and IL-17A+ CD8+ T cell subsets compared to healthy children. Cytokine-producing T cell subsets were predominantly CD45RA+CCR7+ TNAIVE-LIKE cells, yet PD-1, a marker of persistent activation/exhaustion, was more highly expressed by the central memory (TCM) and effector memory (TEM) T cell subsets. In summary, our study suggests that IL-10 mediated immune regulation and depletion of IFN-γ+ EBNA1-specific CD4+ T cells are complementary mechanisms that contribute to impaired T cell cytotoxicity in eBL pathogenesis.

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The differential immune responses to COVID-19 in peripheral and lung revealed by single-cell RNA sequencing

10.1101/2020.08.15.20175638 ◽

2020 ◽

Author(s):

Gang Xu ◽

Furong Qi ◽

Hanjie Li ◽

Qianting Yang ◽

Haiyan Wang ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Single Cell ◽

Mononuclear Cells ◽

Immune Cell ◽

Close Association ◽

Suppressor Cells ◽

T Cell Subsets ◽

Peripheral Blood Mononuclear ◽

Peripheral T Cells

Understanding the mechanism that leads to immune dysfunction induced by SARS-CoV2 virus is crucial to develop treatment for severe COVID-19. Here, using single cell RNA-seq, we characterized the peripheral blood mononuclear cells (PBMC) from uninfected controls and COVID-19 patients, and cells in paired broncho-alveolar lavage fluid (BALF). We found a close association of decreased dendritic cells (DC) and increased monocytes resembling myeloid-derived suppressor cells (MDSC) which correlated with lymphopenia and inflammation in the blood of severe COVID-19 patients. Those MDSC-like monocytes were immune-paralyzed. In contrast, monocyte-macrophages in BALFs of COVID-19 patients produced massive amounts of cytokines and chemokines, but secreted little interferons. The frequencies of peripheral T cells and NK cells were significantly decreased in severe COVID-19 patients, especially for innate-like T and various CD8+ T cell subsets, compared to health controls. In contrast, the proportions of various activated CD4+ T cell subsets, including Th1, Th2 and Th17-like cells were increased and more clonally expanded in severe COVID-19 patients. Patients' peripheral T cells showed no sign of exhaustion or augmented cell death, whereas T cells in BALFs produced higher levels of IFNG, TNF, CCL4 and CCL5 etc. Paired TCR tracking indicated abundant recruitment of peripheral T cells to the patients' lung. Together, this study comprehensively depicts how the immune cell landscape is perturbed in severe COVID-19.

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Immune Modulation of Platelet-Derived Mitochondria on Memory CD4+ T Cells in Humans

International Journal of Molecular Sciences ◽

10.3390/ijms21176295 ◽

2020 ◽

Vol 21 (17) ◽

pp. 6295

Author(s):

Haibo Yu ◽

Wei Hu ◽

Xiang Song ◽

Yong Zhao

Keyword(s):

T Cells ◽

Cd4 T Cells ◽

Immune Modulation ◽

Mononuclear Cells ◽

Effector Memory ◽

Gene Expressions ◽

Peripheral Blood Mononuclear ◽

Immune Modulators ◽

Cd28 Bead ◽

Stromal Cell Derived Factor

CD4+ T cells are one of the key immune cells contributing to the immunopathogenesis of type 1 diabetes (T1D). Previous studies have reported that platelet-derived mitochondria suppress the proliferation of peripheral blood mononuclear cells (PBMC). To further characterize the immune modulation of platelet-derived mitochondria, the purified CD4+ T cells were treated, respectively, with platelet-derived mitochondria. The data demonstrated that MitoTracker Deep Red-labeled platelet-derived mitochondria could directly target CD4+ T cells through C-X-C motif chemokine receptor 4 (CXCR4) and its ligand stromal cell-derived factor-1 (SDF-1), regulating the anti-CD3/CD28 bead-activated CD4+ T cells. The result was an up-regulation of Naïve and central memory (TCM) CD4+ T cells, the down-regulation of effector memory (TEM) CD4+ T cells, and modulations of cytokine productions and gene expressions. Thus, platelet-derived mitochondria have a translational potential as novel immune modulators to treat T1D and other autoimmune diseases.

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343. T-cell Subsets Associated with Diabetes in Veterans with and without HIV

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.416 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S182-S183

Author(s):

Samuel Bailin ◽

Kathleen McGinnis ◽

Wyatt J McDonnell ◽

Kaku So-Armah ◽

Melissa Wellons ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Cd8 T Cells ◽

Immune Activation ◽

Cd4 T Cells ◽

T Cell Subsets ◽

Effector Memory ◽

Hiv Status ◽

Adaptive Immune ◽

Memory Cd4 T Cells

Abstract Background Depletion of naïve CD4+ T cells and elevated adaptive immune activation are hallmarks of HIV infection. Higher proportions of memory CD4+ T cells are associated with prevalent diabetes in the general population, but few studies of persons with HIV (PWH) exist. Methods We analyzed data from 1532 PWH and 836 uninfected veterans in the longitudinal Veterans Aging Cohort Study (VACS), which archived peripheral mononuclear cells from these veterans between 2005 and 2007. We used flow cytometry to phenotype CD4+ and CD8+ T cells, including naïve, activated CD38+, senescent CD57+, total memory, and memory subsets. Prevalent diabetes (at blood collection) was identified in the VA electronic medical record using random glucose, hemoglobin A1c, ICD-9 codes, and medication. Cases were validated by two-physician chart review. We used multivariate logistic regression models adjusted for age, gender, body mass index, race/ethnicity, unhealthy alcohol use, hepatitis C, CMV status, and viral suppression stratified by HIV status to identify T-cell subsets associated with diabetes in PWH and uninfected. Results The cohort was 95% male, 68% African-American, and 22% diabetic. Higher CD4+CD45RO+ memory T cells were associated with prevalent diabetes in the uninfected and in PWH (P = 0.03 and P = 0.07, respectively; Figure A). Among subsets, diabetes was associated with higher transitional memory CD4+ T cells in the uninfected (P = 0.01), but higher central memory cells (P = 0.02) and lower effector memory cells (P = 0.04) in PWH. T effector memory RA+ cells were not associated with diabetes. Lower senescent CD4+CD57+ T cells were associated with diabetes in both PWH and uninfected (P = 0.03 and P = 0.04, respectively; Figure B), but results for naïve CD8+ T cells diverged: diabetes was associated with higher naïve CD8+cells in PWH but lower in uninfected (P = 0.01 and P < 0.01, respectively; Figure C). We assessed interaction by HIV status in a pooled model, which was only significant for the naïve CD8+ T cells (P = 0.01). Conclusion The adaptive immune profile associated with prevalent diabetes was similar by HIV status and characterized by a shift in CD4+ T cells from senescent to memory phenotypes, suggesting that chronic immune activation contributes to the higher risk of diabetes in PWH. Disclosures All authors: No reported disclosures.

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