Tissue Resident CD8+T-cells as mediators of protective immunity in breastmilk transmission of HCMV.

While the role of breastmilk antibodies to protect infants from CMV has been investigated, the role of T-cells, have received little attention. We compared the frequency of memory T-cell populations in breastmilk between mothers of infants who acquired breastmilk HCMV (transmitters) and those with uninfected infants (non-transmitters). Non-transmitter moms had an increased frequency of CD8+ effector memory T-cells (Tem) in their breastmilk.

Interferon-γ Responses to Chlamydia trachomatis Vaccine Candidate Proteins in Women With Different Chlamydia Outcomes.

Background: Chlamydia trachomatis testing and treatment strategies have not decreased infection rates, justifying need for a chlamydia vaccine. A murine study showed that a vaccine consisting of major outer membrane protein (MOMP) and polymorphic membrane proteins (Pmps) E, F, G, and H elicited protective immunity; studies on human cellular immune responses to Pmps are sparse.

Methods: Interferon gamma (IFN-γ) responses to these 5 proteins were measured by ELISPOT in peripheral blood mononuclear cells from women returning for treatment of a positive chlamydia test.

Brief Report: Intracellular Cystatin B Levels Are Altered in HIV-Infected Participants With Respect to Neurocognitive Status and Antiretroviral Therapy.

With advances in HIV treatment, people with HIV (PWH) are living longer but experience aging-related comorbidities, including cognitive deficits, at higher rates than the general population. Previous studies have shown alterations in lysosomal proteins in blood from PWH with severe dementia. However, these markers have not been evaluated in PWH with milder neurocognitive impairment.

Duration of post-COVID-19 symptoms is associated with sustained SARS-CoV-2-specific immune responses.

A subset of COVID-19 patients exhibit post-acute sequelae of COVID-19 (PASC), but little is known about the immune signatures associated with these syndromes. We investigated longitudinal peripheral blood samples in 50 individuals with previously confirmed SARS-CoV-2 infection, including 20 who experienced prolonged duration of COVID-19 symptoms (lasting more than 30 days; median = 74 days) compared with 30 who had symptom resolution within 20 days. Individuals with prolonged symptom duration maintained antigen-specific T cell response magnitudes to SARS-CoV-2 spike protein in CD4+ and circulating T follicular helper cell populations during late convalescence, while those without persistent symptoms demonstrated an expected decline.

Extensive proteomic and transcriptomic changes quench the TCR/CD3 activation signal of latently HIV-1 infected T cells.

The biomolecular mechanisms controlling latent HIV-1 infection, despite their importance for the development of a cure for HIV-1 infection, are only partially understood. For example, ex vivo studies have recently shown that T cell activation only triggered HIV-1 reactivation in a fraction of the latently infected CD4+ T cell reservoir, but the molecular biology of this phenomenon is unclear. We demonstrate that HIV-1 infection of primary T cells and T cell lines indeed generates a substantial amount of T cell receptor (TCR)/CD3 activation-inert latently infected T cells.

Sustained cellular immune dysregulation in individuals recovering from SARS-CoV-2 infection.

SARS-CoV-2 causes a wide spectrum of clinical manifestations and significant mortality. Studies investigating underlying immune characteristics are needed to understand disease pathogenesis and inform vaccine design. In this study, we examined immune cell subsets in hospitalized and nonhospitalized individuals.

The tetraspanin CD151 marks a unique population of activated human T cells.

Tetraspanins are a family of proteins with an array of functions that are well studied in cancer biology, but their importance in immunology is underappreciated. Here we establish the tetraspanin CD151 as a unique marker of T-cell activation and, in extension, an indicator of elevated, systemic T-cell activity. Baseline CD151 expression found on a subset of T-cells was indicative of increased activation of the MAPK pathway.

Evaluation of Mucosal Humoral and Cellular Immune Responses to HIV in External Secretions and Mucosal Tissues.

The mucosal immune systems of the genital and intestinal tracts as the most frequent sites of HIV-1 entry, display remarkable immunological differences from the systemic immune compartment which must be considered in the evaluation of humoral and cellular immune responses to HIV-1. Marked differences in the fluids from the genital and intestinal tracts and in plasma with respect to the Ig isotypes, their levels, molecular forms and distinct effector functions must be taken into consideration in the evaluation and interpretation of humoral immune responses. Because of the low levels and highly pronounced variation in Ig content, HIV-1-specific antibody concentrations should be always related to the levels of total Ig of a given isotype.

T cell phenotypes in women with Chlamydia trachomatis infection and influence of treatment on phenotype distributions.

T cell phenotypes involved in the immune response to Chlamydia trachomatis (CT) have not been fully elucidated in humans. We evaluated differences in T cell phenotypes between CT-infected women and CT-seronegative controls and investigated changes in T cell phenotype distributions after CT treatment and their association with reinfection. We found a higher expression of T cell activation markers (CD38HLA-DR), T helper type 1 (Th1)- and Th2-associated effector phenotypes (CXCR3CCR5 and CCR4, respectively), and T cell homing marker (CCR7) for both CD4 and CD8 T cells in CT-infected women.

Breast Milk Human Cytomegalovirus (CMV) Viral Load and the Establishment of Breast Milk CMV-pp65-Specific CD8 T Cells in Human CMV Infected Mothers.

The role of human cytomegalovirus (HCMV)-specific T-cell responses in breast milk of HCMV-seropositive mothers is not well defined. In these studies, we demonstrate that the frequency of cytomegalovirus (CMV)-pp65-specific T-cell responses in peripheral blood mononuclear cells (PBMCs) and breast milk cells (BMCs) is increased for CD8+ T cells in both sample sources when compared with CD4+ T cells. The frequency of pp55-specific CD8 T cells producing interferon γ (IFN-γ) alone or dual IFN-γ/granzyme rB producers is increased in breast milk compared with PBMCs.

CD151 Expression Is Associated with a Hyperproliferative T Cell Phenotype.

The tetraspanin CD151 is a marker of aggressive cell proliferation and invasiveness for a variety of cancer types. Given reports of CD151 expression on T cells, we explored whether CD151 would mark T cells in a hyperactivated state. Consistent with the idea that CD151 could mark a phenotypically distinct T cell subset, it was not uniformly expressed on T cells.

Distinct peripheral vs mucosal T-cell phenotypes in chlamydia-infected women.

Problem: Differences in circulating (peripheral) and mucosal T-cell phenotypes in chlamydia-infected women remain largely unknown.

Method Of Study: Thirteen paired mononuclear cell specimens from blood and cervicovaginal lavages collected from chlamydia-infected women were stained and analyzed using ten-color cell surface flow cytometry for T-cell distribution, activation status, homing, and T helper (Th)-associated chemokine receptors (CKRs).

Results: A higher proportion of genital mucosal T-cells were activated (CD38 HLA-DR ) and expressed CCR5 and Th1-associated CKR CXCR3 CCR5 compared to peripheral T-cells, but a lower proportion of mucosal T-cells expressed homing CKR CCR7, Th-2 associated CKR CCR4, and CXCR3 CCR4 for both T-cell subsets.

Diminished CD103 (αEβ7) Expression on Resident T Cells from the Female Genital Tract of HIV-Positive Women.

Background: Tissue resident memory T cells (TrM) provide an enhanced response against infection at mucosal surfaces, yet their function has not been extensively studied in humans, including the female genital tract (FGT).

Methods: Using polychromatic flow cytometry, we studied TrM cells, defined as CD62L-CCR7-CD103CD69 CD4 and CD8 T cells in mucosa-derived T cells from healthy and HIV-positive women.

Results: We demonstrate that TrM are present in the FGT of healthy and HIV-positive women.

The Predominant CD4 Th1 Cytokine Elicited to Chlamydia trachomatis Infection in Women Is Tumor Necrosis Factor Alpha and Not Interferon Gamma.

infection is the most prevalent bacterial sexually transmitted infection and can cause significant reproductive morbidity in women. There is insufficient knowledge of -specific immune responses in humans, which could be important in guiding vaccine development efforts. In contrast, murine models have clearly demonstrated the essential role of T helper type 1 (Th1) cells, especially interferon gamma (IFN-γ)-producing CD4 T cells, in protective immunity to chlamydia.

Epitope Capsid-Incorporation: New Effective Approach for Vaccine Development for Chagas Disease.

Background: Previously we reported that a hexon-modified adenovirus (Ad) vector containing the invasive neutralizing epitope of ( trypomastigote gp83 (Ad5-gp83) provided immunoprotection against infection. The purpose of this work was to design an improved vaccine for using a novel epitope capsid incorporation strategy. Thus, we evaluated the immunoprotection raised by co-immunization with Ad5-gp83 and an Ad vector containing an epitope (ASP-M) of the amastigote surface protein 2.

HIV-1 latency and virus production from unintegrated genomes following direct infection of resting CD4 T cells.

Background: HIV-1 integration is prone to a high rate of failure, resulting in the accumulation of unintegrated viral genomes (uDNA) in vivo and in vitro. uDNA can be transcriptionally active, and circularized uDNA genomes are biochemically stable in non-proliferating cells. Resting, non-proliferating CD4 T cells are prime targets of HIV-1 infection and latently infected resting CD4 T cells are the major barrier to HIV cure.

Brief Report: Enhanced Allogeneic Cellular Responses to Mismatched HLA-B Antigens Results in More Efficient Killing of HIV Infected Cells.

Epidemiologic studies have demonstrated that HIV-1 discordant couples who share HLA-B alleles were more likely to transmit HIV-1. These data lead us to hypothesize that individuals who match at both HLA-B alleles should have a reduced allogeneic response than those who are not matched. We observed diminished killing of CD4 target cells only when HLA-B alleles were matched.

Stable Phenotypic Changes of the Host T Cells Are Essential to the Long-Term Stability of Latent HIV-1 Infection.

Unlabelled: The extreme stability of the latent HIV-1 reservoir in the CD4(+) memory T cell population prevents viral eradication with current antiretroviral therapy. It has been demonstrated that homeostatic T cell proliferation and clonal expansion of latently infected T cells due to viral integration into specific genes contribute to this extraordinary reservoir stability. Nevertheless, given the constant exposure of the memory T cell population to specific antigen or bystander activation, this reservoir stability seems remarkable, unless it is assumed that latent HIV-1 resides exclusively in memory T cells that recognize rare antigens.

Immune activation is associated with CD8 T cell interleukin-21 production in HIV-1-infected individuals.

Interleukin-21 (IL-21) can be produced by CD8 T cells from HIV-1-infected individuals and those with autoimmune disease, but the mechanism remains poorly understood. Here we demonstrate that IL-21-producing CD8 T cells are not associated with CD4 depletion and are absent in patients with idiopathic CD4 lymphocytopenia. Instead, IL-21 production by CD8 T cells was associated with high levels of activation, suggesting that these cells emerge as a consequence of excessive chronic immune activation rather than CD4 lymphopenia.

Therapeutic efficacy of suppressing the Jak/STAT pathway in multiple models of experimental autoimmune encephalomyelitis.

Pathogenic Th cells and myeloid cells are involved in the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The JAK/STAT pathway is used by numerous cytokines for signaling and is critical for development, regulation, and termination of immune responses. Dysregulation of the JAK/STAT pathway has pathological implications in autoimmune and neuroinflammatory diseases.

Dimorphic HLA-B signal peptides differentially influence HLA-E- and natural killer cell-mediated cytolysis of HIV-1-infected target cells.

As a mechanism of self-protection, signal peptides cleaved from human leukocyte antigen (HLA) class I products bind to HLA-E before the complex interacts with the natural killer (NK) cell receptor CD94/NKG2A to inhibit NK-mediated cell lysis. Two types of the signal peptides differ in their position 2 (P2) anchor residue, with P2-methionine (P2-M) having higher HLA-E binding affinity than P2-threonine (P2-T). All HLA-A and HLA-C molecules carry P2-M, whereas HLA-B products have either P2-M or P2-T.

HIV-specific CD8+ T cells from elite controllers are primed for survival.

HIV-specific cytotoxic T lymphocytes (CTL) are preferentially primed for apoptosis, and this may represent a viral escape mechanism. We hypothesized that HIV-infected individuals that control virus to undetectable levels without antiretroviral therapy (ART) (elite controllers [EC]) have the capacity to upregulate survival factors that allow them to resist apoptosis. To address this, we performed cross-sectional and longitudinal analysis of proapoptotic (cleaved caspase-3) and antiapoptotic (Bcl-2) markers of cytomegalovirus (CMV) and HIV-specific CD8 T cells in a cohort of HIV-infected subjects with various degrees of viral control on and off ART.

Hormonal contraception and HIV-1 infection: medroxyprogesterone acetate suppresses innate and adaptive immune mechanisms.

Recent observational studies indicate an association between the use of hormonal contraceptives and acquisition and transmission of HIV-1. The biological and immunological mechanisms underlying the observed association are unknown. Depot medroxyprogesterone acetate (DMPA) is a progestin-only injectable contraceptive that is commonly used in regions with high HIV-1 prevalence.

Host factor transcriptional regulation contributes to preferential expression of HIV type 1 in IL-4-producing CD4 T cells.

HIV type 1 (HIV-1) replicates preferentially in IL-4-producing CD4 T cells for unclear reasons. We show increased HIV-1 expression is irrespective of viral tropism for chemokine receptors as previously suggested, but rather transcription of the HIV-1 long terminal repeat (LTR) is increased in IL-4-producing CD4 T cells. Increased expression of HIV-1 message is also confirmed in IL-4-producing CD4 T cells from HIV-1-infected individuals ex vivo.