Publications by authors named "Smita S Iyer"

Integrin αβ+ T cells perpetuate tissue injury in chronic inflammatory diseases, yet their role in hepatic fibrosis progression remains poorly understood. Here, we report increased accumulation of αβ+ T cells in the liver of people with cirrhosis relative to disease controls. Similarly, hepatic fibrosis in the established mouse model of CCl-induced liver fibrosis was associated with enrichment of intrahepatic αβ+ CD4 and CD8 T cells.

View Article and Find Full Text PDF
Article Synopsis
  • CD4+ T cells in the brain help maintain immune balance, but their specific roles and abilities are still being studied.
  • Using various analysis techniques, researchers discovered a unique group of CD4+ T cells that share characteristics with central memory cells found in lymph nodes, showing they can effectively respond to immune challenges.
  • The study also found that when TCM cells are trapped in lymph nodes, they decrease in the brain's cerebrospinal fluid, indicating their importance in monitoring brain immune health, especially during chronic infections.
View Article and Find Full Text PDF

CD4 T follicular helper cells (T) are essential for establishing serological memory and have distinct helper attributes that impact both the quantity and quality of the antibody response. Insights into T subsets that promote antibody persistence and functional capacity can critically inform vaccine design. Based on the T profiles evoked by the live attenuated measles virus vaccine, renowned for its ability to establish durable humoral immunity, we investigated the potential of a T1/17 recall response during the boost phase to enhance persistence of HIV-1 Envelope (Env) antibodies in rhesus macaques.

View Article and Find Full Text PDF

Virologic suppression with antiretroviral therapy (ART) has significantly improved health outcomes for people living with HIV, yet challenges related to chronic inflammation in the central nervous system (CNS)-known as Neuro-HIV- persist. As primary targets for HIV-1 with the ability to survey and populate the CNS and interact with myeloid cells to co-ordinate neuroinflammation, CD4 T cells are pivotal in Neuro-HIV. Despite their importance, our understanding of CD4 T cell distribution in virus-targeted CNS tissues, their response to infection, and potential recovery following initiation of ART remain limited.

View Article and Find Full Text PDF

HCMV vaccine development has traditionally focused on viral antigens identified as key targets of neutralizing antibody (NAb) and/or T cell responses in healthy adults with chronic HCMV infection, such as glycoprotein B (gB), the glycoprotein H-anchored pentamer complex (PC), and the unique long 83 (UL83)-encoded phosphoprotein 65 (pp65). However, the protracted absence of a licensed HCMV vaccine that reduces the risk of infection in pregnancy regardless of serostatus warrants a systematic reassessment of assumptions informing vaccine design. To illustrate this imperative, we considered the hypothesis that HCMV proteins detected as targets of T cell responses may contain important vaccine antigens.

View Article and Find Full Text PDF

Unlabelled: CD4 T cells survey and maintain immune homeostasis in the brain, yet their differentiation states and functional capabilities remain unclear. Our approach, combining single-cell transcriptomic analysis, ATAC-seq, spatial transcriptomics, and flow cytometry, revealed a distinct subset of CCR7+ CD4 T cells resembling lymph node central memory (T ) cells. We observed chromatin accessibility at the CCR7, CD28, and BCL-6 loci, defining molecular features of T .

View Article and Find Full Text PDF

Virologic suppression with antiretroviral therapy (ART) has significantly improved health outcomes for people living with HIV, yet challenges related to chronic inflammation in the central nervous system (CNS) - known as Neuro-HIV- persist. As primary targets for HIV-1 with the ability to survey and populate the CNS and interact with myeloid cells to co-ordinate neuroinflammation, CD4 T cells are pivotal in Neuro-HIV. Despite their importance, our understanding of CD4 T cell distribution in virus-targeted CNS tissues, their response to infection, and potential recovery following initiation of ART remain limited.

View Article and Find Full Text PDF

CD4 T follicular helper cells (Tfh) are essential for establishing serological memory and have distinct helper attributes that impact both the quantity and quality of the antibody response. Insights into Tfh subsets that promote antibody persistence and functional capacity can critically inform vaccine design. Based on the Tfh profiles evoked by the live attenuated measles virus vaccine, renowned for its ability to establish durable humoral immunity, we investigated the potential of a Tfh1/17 recall response during the boost phase to enhance persistence of HIV-1 Envelope (Env) antibodies in rhesus macaques.

View Article and Find Full Text PDF

Background And Aims: The immunosuppressive T regulatory cells (Tregs) regulate immune responses and maintain immune homeostasis, yet their functions in nonalcoholic fatty liver disease (NAFLD) pathogenesis remains controversial.

Methods: Mice were fed a normal diet (ND) or a western diet (WD) for 16 weeks to induce NAFLD. Diphtheria toxin injection to deplete Tregs in Foxp3 mice or Treg induction therapy in WT mice to augment Treg numbers was initiated at twelve and eight weeks, respectively.

View Article and Find Full Text PDF

Integrin α β + T cells perpetuate tissue injury in chronic inflammatory diseases, yet their role in hepatic fibrosis progression remains poorly understood. Here we report increased accumulation of α β + T cells in the liver of people with cirrhosis relative to disease controls. Similarly, hepatic fibrosis in the established mouse model of CCl -induced liver fibrosis was associated with enrichment of intrahepatic α β + CD4 and CD8 T cells.

View Article and Find Full Text PDF

The global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated coronavirus disease (COVID-19) has led to a pandemic of unprecedented scale. An intriguing feature of the infection is the minimal disease in most children, a demographic at higher risk for other respiratory viral diseases. To investigate age-dependent effects of SARS-CoV-2 pathogenesis, we inoculated two rhesus macaque monkey dam-infant pairs with SARS-CoV-2 and conducted virological and transcriptomic analyses of the respiratory tract and evaluated systemic cytokine and Ab responses.

View Article and Find Full Text PDF
Article Synopsis
  • The FDA authorized BNT162b2 and mRNA-1273 vaccines for infants 6 months and older in June 2022, but concerns about their long-term efficacy against new variants remain.
  • Previous studies shown that specific vaccine formulations were safe and effective in infant rhesus macaques, demonstrating persistent antibody responses for 12 months.
  • When challenged with the Delta variant, vaccinated macaques showed better viral clearance and milder symptoms compared to unvaccinated ones, suggesting that early-life vaccination against SARS-CoV-2 can be beneficial.
View Article and Find Full Text PDF

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), can induce a plethora of neurological complications in some patients. However, it is still under debate whether SARS-CoV-2 directly infects the brain or whether CNS sequelae result from systemic inflammatory responses triggered in the periphery. By using high-resolution microscopy, we investigated whether SARS-CoV-2 reaches the brain and how viral neurotropism can be modulated by aging in a non-human primate model of COVID-19.

View Article and Find Full Text PDF
Article Synopsis
  • The study examines how immune activation in the central nervous system (CNS) during chronic infections like HIV-1 can lead to neurodegeneration and cognitive decline, highlighting the importance of understanding acute immune responses.
  • Researchers investigated molecular changes in brain areas vulnerable to neuroAIDS and cognitive impairment in rhesus macaques infected with SHIV.C.CH505.
  • Findings revealed that after infection, there were significant changes in gene expression related to immune responses in specific brain regions, particularly the pre-frontal cortex and superior temporal sulcus, indicating a strong immune activation that could impact cognitive and motor functions.
View Article and Find Full Text PDF

A subgroup among people living with HIV (PLHIV) experience viral suppression, sometimes to an undetectable level in the blood and/or are able to maintain a healthy CD4+ T-cell count without the influence of antiretroviral (ARV) therapy. One out of three hundred PLHIV fall into this category, and a large sample of this group can be found in areas with a high prevalence of HIV infection such as Nigeria and South Africa. Understanding the mechanism underpinning the nonprogressive phenotype in this subgroup may provide insights into the control of the global HIV epidemic.

View Article and Find Full Text PDF
Article Synopsis
  • - Early in the pandemic, there was hope that convalescent plasma from COVID-19 survivors would effectively treat hospitalized patients, but later controlled trials showed only moderate efficacy, especially when used early in infection.
  • - In a study, 12 adult rhesus macaques were infected with SARS-CoV-2 and then given either high-titer convalescent plasma or normal plasma; the results showed only slight benefits, with similar viral loads but reduced infectious virus in the lungs for those treated with convalescent plasma.
  • - Overall, the benefits of convalescent plasma were marginal compared to monoclonal antibodies, and the study highlights the need for improved animal models to test new treatment strategies against SARS-CoV-
View Article and Find Full Text PDF

Human clinical studies investigating use of convalescent plasma (CP) for treatment of coronavirus disease 2019 (COVID-19) have produced conflicting results. Outcomes in these studies may vary at least partly due to different timing of CP administration relative to symptom onset. The mechanisms of action of CP include neutralizing antibodies but may extend beyond virus neutralization to include normalization of blood clotting and dampening of inflammation.

View Article and Find Full Text PDF

Anti-viral monoclonal antibody (mAb) treatments may provide immediate but short-term immunity from coronavirus disease 2019 (COVID-19) in high-risk populations, such as people with diabetes and the elderly; however, data on their efficacy in these populations are limited. We demonstrate that prophylactic mAb treatment blocks viral replication in both the upper and lower respiratory tracts in aged, type 2 diabetic rhesus macaques. mAb infusion dramatically curtails severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated stimulation of interferon-induced chemokines and T cell activation, significantly reducing development of interstitial pneumonia.

View Article and Find Full Text PDF

Unlabelled: Early in the SARS-CoV-2 pandemic, there was a high level of optimism based on observational studies and small controlled trials that treating hospitalized patients with convalescent plasma from COVID-19 survivors (CCP) would be an important immunotherapy. However, as more data from controlled trials became available, the results became disappointing, with at best moderate evidence of efficacy when CCP with high titers of neutralizing antibodies was used early in infection. To better understand the potential therapeutic efficacy of CCP, and to further validate SARS-CoV-2 infection of macaques as a reliable animal model for testing such strategies, we inoculated 12 adult rhesus macaques with SARS-CoV-2 by intratracheal and intranasal routes.

View Article and Find Full Text PDF

HIV preferentially infects α β CD4 T cells, forming latent reservoirs that contribute to HIV persistence during antiretroviral therapy. However, the properties of α β CD4 T cells in blood and mucosal compartments remain understudied. Employing two distinct models of HIV infection, HIV-infected humans and simian-human immunodeficiency virus (SHIV)-infected rhesus macaques, we show that α β CD4 T cells in blood are enriched for genes regulating cell cycle progression and cellular metabolism.

View Article and Find Full Text PDF

There is an urgent need for effective therapeutic interventions against SARS-CoV-2, including new variants that continue to arise. Neutralizing monoclonal antibodies have shown promise in clinical studies. We investigated the therapeutic efficacy of a combination of two potent monoclonal antibodies, C135-LS and C144-LS that carry half-life extension mutations, in the rhesus macaque model of COVID-19.

View Article and Find Full Text PDF

Although antiretroviral therapy suppresses HIV replication, it does not eliminate viral reservoirs or restore damaged lymphoid tissue, posing obstacles to HIV eradication. Using the SIV model of AIDS, we investigated the effect of mesenchymal stem/stromal cell (MSC) infusions on gut mucosal recovery, antiviral immunity, and viral suppression and determined associated molecular/metabolic signatures. MSC administration to SIV-infected macaques resulted in viral reduction and heightened virus-specific responses.

View Article and Find Full Text PDF

CD4 T follicular helper (T) cells are important for the generation of durable and specific humoral protection against viral infections. The degree to which SARS-CoV-2 infection generates T cells and stimulates the germinal center (GC) response is an important question as we investigate vaccine induced immunity against COVID-19. Here, we report that SARS-CoV-2 infection in rhesus macaques, either infused with convalescent plasma, normal plasma, or receiving no infusion, resulted in transient accumulation of pro-inflammatory monocytes and proliferating T cells with a T1 profile in peripheral blood.

View Article and Find Full Text PDF

CD4 T follicular helper (T ) cells are important for the generation of long-lasting and specific humoral protection against viral infections. The degree to which SARS-CoV-2 infection generates T cells and stimulates the germinal center response is an important question as we investigate vaccine options for the current pandemic. Here we report that, following infection with SARS-CoV-2, adult rhesus macaques exhibited transient accumulation of activated, proliferating T cells in their peripheral blood on a transitory basis.

View Article and Find Full Text PDF

Background: The emergence of SARS-CoV-2 and the ensuing COVID-19 pandemic prompted the need for a surveillance program to determine the viral status of the California National Primate Research Center non-human primate breeding colony, both for reasons of maintaining colony health and minimizing the risk of interference in COVID-19 and other research studies.

Methods: We collected biological samples from 10% of the rhesus macaque population for systematic testing to detect SARS-CoV-2 virus by RT-PCR and host antibody response by ELISA. Testing required the development and validation of new assays and an algorithm using in laboratory-developed and commercially available reagents and protocols.

View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Notice

Message: fwrite(): Write of 34 bytes failed with errno=28 No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 272

Backtrace:

A PHP Error was encountered

Severity: Warning

Message: session_write_close(): Failed to write session data using user defined save handler. (session.save_path: /var/lib/php/sessions)

Filename: Unknown

Line Number: 0

Backtrace: