scholarly journals 3160 The Effects of Aging on the Rectal Mucosal CD4+ T cell Compartment and its Implications for HIV Transmission

2019 ◽  
Vol 3 (s1) ◽  
pp. 115-116
Author(s):  
Cassie Grimsley Ackerley ◽  
Praveen Kumar Amancha ◽  
Phillip M. Murray ◽  
Jasper Barnes ◽  
Colleen F. Kelley
Keyword(s):  
Target Cell ◽  
Hiv Transmission ◽  
Rectal Mucosa ◽  
Rectal Biopsy ◽  
Study Groups ◽  
Cd4 T Cell ◽  
Hiv Susceptibility ◽  
Biopsy Specimens ◽  
Effects Of Aging ◽  
Hiv Negative

OBJECTIVES/SPECIFIC AIMS: In the first aim, we will evaluate the proportion of highly HIV-susceptible memory CD4+ T cells present in the rectal mucosa, based on the proliferation status and expression of the HIV susceptibility markers, CCR5 and α4β7, between HIV-negative adolescent MSM and adult MSM engaging in RAI. The second aim will assess differences between the two study groups in the ratio of Th17 cells (CD4+ IL17+) to Treg cells (CD4+ FoxP3+ CD25+) in the rectal mucosa as a determinant of mucosal inflammation. Finally, in the third aim, we will utilize ex vivo rectal biopsy explant challenge experiments to examine whether HIV target cell availability and the Th17/Treg ratio influence rectal mucosal HIV susceptibility. METHODS/STUDY POPULATION: Rectal biopsy specimens are being collected from healthy, HIV-negative men that comprise the two study groups: 40 adolescent MSM 18-21 years of age who have engaged in RAI at least once previously in their lifetime and 40 adult MSM ≥35 years of age who have engaged in RAI for the previous 5 consecutive years with a minimum of 12 episodes annually. To identify CD4+ subsets of interest for aims 1 and 2, rectal mucosal mononuclear cells are isolated and phenotyped with CD45, CD3, CD4, CD45RA, CCR7, CD69, CCR5, α4β7, Ki67, FOXP3, and CD25 antibodies. To identify the Th17 cell subtype, the cells are stimulated with PMA/Ionamycin and stained with an antibody specific to IL-17A. Using cross-sectional analyses, we will compare the frequencies of mucosal CD4+ T cells that express certain phenotypic characteristics and evaluate differences in the Th17/Treg ratio between adolescent and adult MSM. For aim 3, rectal biopsy specimens are inoculated with HIV virus and the culture supernatant is assayed for p24 concentration on days 3, 7, 10 14, and 18. Longitudinal analyses will be performed to detect differences in p24 concentration at each time point and assess associations with mucosal target cell availability and with the Th17/Treg ratio. RESULTS/ANTICIPATED RESULTS: We hypothesize that younger age will be associated with enhanced memory CD4+ T cell proliferation and increased expression of HIV susceptibility markers (CCR5 and/or α4β7). In addition, we expect that the rectal mucosa of adolescent MSM will demonstrate a higher Th17/Treg ratio as compared to adult MSM, which could facilitate HIV transmission. It is also anticipated that rectal mucosal immune phenotypes characterized by increased HIV target cell availability and high Th17/Treg ratios will be associated with enhanced mucosal HIV susceptibility in the explant challenge model. DISCUSSION/SIGNIFICANCE OF IMPACT: There is a paucity of information regarding the mechanisms of rectal HIV transmission, and no studies to date investigate the immunologic effects of aging on transmission in the rectal mucosa. The results from this study will provide important information regarding age-related differences in the immune cell composition of the rectal mucosa as a critical step in better understanding immunologic factors that influence rectal HIV transmission.

scholarly journals The rectal mucosa and condomless receptive anal intercourse in HIV-negative MSM: implications for HIV transmission and prevention

2016 ◽  
Vol 10 (4) ◽  
pp. 996-1007 ◽  
Author(s):  
C F Kelley ◽  
C S Kraft ◽  
T JB de Man ◽  
C Duphare ◽  
H-W Lee ◽  
...  
Keyword(s):  
Hiv Transmission ◽  
Rectal Mucosa ◽  
Anal Intercourse ◽  
Receptive Anal Intercourse ◽  
Hiv Negative

scholarly journals Influence of two different fixatives on the identification of plasma cells in human rectal mucosa.

1980 ◽  
Vol 28 (9) ◽  
pp. 1018-1020 ◽  
Author(s):  
M F Heyworth
Keyword(s):  
Plasma Cells ◽  
Rectal Mucosa ◽  
Rectal Biopsy ◽  
Immunoperoxidase Technique ◽  
Biopsy Specimens ◽  
Indirect Immunoperoxidase

Plasma cells in sections of bisected human rectal biopsy specimens, fixed in two alternative fixatives, were enumerated after staining by an indirect immunoperoxidase procedure intended to demonstrate immunoglobulin-containing cells. The counts of immunoperoxidase-positive plasma cells were significantly higher after fixation in formol sublimate than after fixation in formol saline. Formol sublimate appears to be a more reliable fixative than formol saline for specimens of rectal mucosa in which quantitation of plasma cells, stained for intracellular immunoglobulin by an immunoperoxidase technique, is intended.

scholarly journals Drug Use is Associated with Anti-CD4 IgG-mediated CD4+ T Cell Death and Poor CD4+ T Cell Recovery in Viral-suppressive HIV-infected Individuals Under Antiretroviral Therapy

2018 ◽  
Vol 16 (2) ◽  
pp. 143-150 ◽  
Author(s):  
Wei Jiang ◽  
Zhenwu Luo ◽  
Lisa Martin ◽  
Zhuang Wan ◽  
Pingfu Fu ◽  
...  
Keyword(s):  
Cell Death ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Drug Use ◽  
Drug Users ◽  
Study Groups ◽  
Cd4 T Cell ◽  
Cell Recovery ◽  
Cell Counts ◽  
Hiv Negative

Background: The role and mechanism of drug use or abuse in Antiretroviral Therapy (ART)-treated HIV disease are not completely known. Methods: To investigate the impact of drug use on HIV pathogenesis without confounding by HIV replication and ART adherence, we first analyzed the data from our clinical database in 103 HIV+ subjects with viral-suppressed ART treatment by a multiple regression test. Results: We found that HIV+ drug users had lower CD4+ T cell counts but higher CD8+ T cell counts compared to HIV+ non-drug users, and both drug use and nadir CD4+ T cell counts was independently associated with CD4+ T cell recovery after controlling for sex and age. Next, we enrolled individuals from four study groups, HIV-negative and HIV+ subjects without any substance use, HIV-negative and HIV+ subjects with current illicit drug use (either non-injection cocaine or cannabis). All HIV+ subjects were viral-suppressed with ART treatment (≥ 2 years). Notably, HIV+ drug users had increased plasma anti-CD4 IgG levels compared to the other three study groups which were inversely correlated with decreased CD4+ T cell counts only in HIV+ drug users. There was a significant increase in CD4+ T cell recovery following ART in HIV+ non-drug users but not in HIV+ drug users. Anti-CD4 IgGs purified from plasma of HIV+ drug users induced CD4+ T cell death in vitro through Antibody-Dependent Cytotoxicity (ADCC). Conclusion: These results suggest that drug use prevents immune reconstitution in HIV-infected individuals despite long-term ART treatment and viral suppression.

scholarly journals Gliadin activates mucosal cell mediated immunity in cultured rectal mucosa from coeliac patients and a subset of their siblings

Gut ◽  
1998 ◽  
Vol 43 (4) ◽  
pp. 484-489 ◽  
Author(s):  
R Troncone ◽  
G Mazzarella ◽  
N Leone ◽  
M Mayer ◽  
M De Vincenzi ◽  
...  
Keyword(s):  
Rectal Mucosa ◽  
Rectal Biopsy ◽  
Cell Mediated Immunity ◽  
Mucosal Cell ◽  
In Vitro System ◽  
Biopsy Specimens ◽  
Activate Cell ◽  
Cell Adhesion Molecule 1

Background—CD3 and γδ cells in the rectal mucosa increase after local instillation of gluten in children with coeliac disease and in half of their siblings.Aim—To establish an in vitro system for assessing immunological changes induced by gluten in the rectum.Patients and Methods—Rectal biopsy specimens obtained from 13 treated coeliac children, nine of their siblings, and nine controls were cultured in vitro with a peptic-tryptic digest of gliadin or ovalbumin. CD3 and CD25 cells were counted, and the expression of adhesion molecules evaluated.Results—In the lamina propria of coeliac biopsy samples cultured with gliadin, but not in those from controls, the expression of vascular cell adhesion molecule 1 (VCAM-1) was enhanced, and the number of CD25 cells was significantly higher than in those cultured in medium alone; the density of intraepithelial CD3 cells was also significantly higher. No differences were noted in coeliac biopsy specimens cultured with ovalbumin. A discriminant analysis allowed correct classification of all controls and all coeliacs but one, but three of nine siblings were allocated to the coeliac group.Conclusions—Our data confirm that gliadin is able to activate cell mediated immunity in the rectal mucosa in coeliac patients and in a subset of their first degree relatives.

scholarly journals Intimate Partner Violence is Associated with Increased CD4+ T-Cell Activation Among HIV-Negative High-Risk Women

2016 ◽  
Vol 1 (1) ◽  
pp. 193 ◽  
Author(s):  
Ameeta Shivdas Kalokhe ◽  
Chris C. Ibegbu ◽  
Surinder P. Kaur ◽  
Rama R. Amara ◽  
Mary E. Kelley ◽  
...  
Keyword(s):  
Intimate Partner Violence ◽  
T Cell ◽  
High Risk ◽  
Partner Violence ◽  
Intimate Partner ◽  
Cd4 T Cell ◽  
High Risk Women ◽  
Hiv Susceptibility ◽  
Hla Dr ◽  
Hiv Negative

Background: Biological pathways mediating the link between intimate partner violence (IPV) and increased HIV risk remain unexplored. We hypothesized that IPV-induced stress negatively affects HIV systemic immune defenses and aimed to evaluate whether IPV was associated with immune profiles linked to HIV susceptibility: CD4 activation and diminished regulatory T-cell (Treg) frequency.Methods: Seventy-five HIV-negative high-risk women were surveyed regarding their IPV experience. They provided blood, urine, and (if present) genital ulcer samples for cortisol, immune assays, and STI testing. Using flow cytometry, we assessed activated CD4+ T-cell (%HLA-DR+/CD38+) and Treg (%CD4+CD25+FoxP3+) frequencies and phenotyping. Nonparametric tests evaluated the association between IPV and immune outcomes. Multivariate regression explored confounding and moderation of the IPV-CD4 activation pathway.Results: Lifetime IPV was associated with increased CD4+ activation (r=0.331, P=0.004), a shift in CD4+ phenotype from naïve to effector memory (r=0.343, P=0.003), and a decrease in naive (%HLA-DR+/CD45RA-) Treg frequency (r=-0.337, P=0.003). Experiencing IPV over the past year had similar trends. After controlling for sexual IPV, lifetime physical and psychological abuse remained significantly associated with CD4+ activation (P=0.004 and P=0.033, respectively). After controlling for race (the only covariate linked to activation), the lifetime IPV-CD4 activation association remained significant (P=0.012). Alcohol use and depression were identified as potential pathway moderators.Conclusion: Our data is the first to suggest an immune link between IPV and HIV, and may help explain differences at the individual level in HIV susceptibility and response to biological HIV prevention strategies. The association of psychological and physical abuse with CD4 activation independent of sexual abuse further supports the existence of a stress-induced immune pathway.

scholarly journals Lymphocyte subset analysis to evaluate the prognosis of HIV-negative patients with pneumocystis pneumonia

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fan Jin ◽  
Jing Xie ◽  
Huan-ling Wang
Keyword(s):  
T Cell ◽  
Cell Count ◽  
Lymphocyte Subsets ◽  
Nk Cell ◽  
Cd8 T Cell ◽  
Pneumocystis Pneumonia ◽  
Lymphocyte Subset ◽  
Cd4 T Cell ◽  
Cell Counts ◽  
Hiv Negative

Abstract Objectives We analysed the peripheral blood lymphocyte subsets of human immunodeficiency virus (HIV)-negative patients infected with pneumocystis pneumonia (PCP) to determine the relationships between the levels of different types of lymphocytes and the prognosis of patients. Methods We retrospectively reviewed HIV-negative patients with PCP diagnosed in our department. All the eligible patients underwent lymphocyte subset analysis on admission. Results A total of 88 HIV-negative PCP patients were enrolled in the study. In univariate analyses, low CD4+ T cell count, low CD8+ T cell count, and low natural killer cell (NK cell) count were associated with higher in-hospital mortality. CD8+ T cell count ≤300/μL was found to be an independent risk factor for poor prognosis in multivariate logistical regression analysis (p = 0.015, OR = 11.526, 95% CI = 1.597–83.158). Although low CD4+ T cell and NK cell counts were not independent risk factors, the mortality rates of PCP patients decreased as the CD4+ T cell and NK cell counts increased. Conclusion The immune process of Pneumocystis jirovecii infection is complex but important. We propose that lymphocyte subsets could give clinicians a better understanding of patient immune status, helping with the early identification of potentially lethal infections and treatment decision making, such as adjusting the immunosuppressive regimen and choosing an appropriate patient monitoring level.

scholarly journals HIV Risk Behavior and Beliefs of HIV-Seropositive Drug Users

1992 ◽  
Vol 22 (4) ◽  
pp. 833-847 ◽  
Author(s):  
Christina Hartgers ◽  
Pieta Krijnen ◽  
Johanna A.R. van den Hoek ◽  
Roel A. Coutinho ◽  
Joop van der Pligt
Keyword(s):  
Risk Behavior ◽  
Hiv Risk ◽  
Drug Users ◽  
Hiv Transmission ◽  
Hiv Risk Behavior ◽  
Unsafe Sex ◽  
Response Efficacy ◽  
Female Prostitute ◽  
Hiv Seropositive ◽  
Hiv Negative

To assess HIV risk behavior, beliefs, attitudes and intentions among HIV-seropositive drug users (DUs), we studied 122 HIV-positive DUs (including ninety-five current injectors) participating in a longitudinal HIV-study among DUs in Amsterdam. All were familiar with their serostatus. Over a period of four months, 20% of the sample put others at risk of HIV infection, mainly through unsafe sex. Forty-nine percent think they might infect someone with HIV in the future, again mainly through unsafe sex. Although the majority intends to use condoms, self-efficacy and response efficacy is low; that is, many do not think they are able to use condoms when necessary and many have limited confidence in the efficacy of condoms in preventing HIV transmission. Correlates of HIV risk behavior were non-Dutch nationality and being a female prostitute. The results suggest that, next to efforts which aim to prevent new infections among HIV-negative injectors or sexual partners of injectors, prevention efforts should focus on HIV-seropositive DUs or former DUs.

scholarly journals Exploring the Factors Considered by People Living with HIV and Their Partners during Preconception

2016 ◽  
Vol 16 (3) ◽  
pp. 239-246 ◽  
Author(s):  
V. Logan Kennedy ◽  
Micaela Collins ◽  
Mark H. Yudin ◽  
Lena Serghides ◽  
Sharon Walmsley ◽  
...  
Keyword(s):  
Logit Model ◽  
Hiv Transmission ◽  
Horizontal Transmission ◽  
People Living With Hiv ◽  
Relative Importance ◽  
Hiv Status ◽  
Ordered Logit Model ◽  
Living With Hiv ◽  
Shed Light ◽  
Hiv Negative

Data are lacking on factors that may impact conception-related decision-making among individuals living with HIV. This study’s aim was to shed light on these considerations. Participants were invited to complete a survey on preconception considerations. A rank-ordered logit model was fit to estimate the relative importance of listed consideration factors; the interaction of HIV status and the factors was assessed. Fifty-nine participants living with HIV and 18 partners (11 HIV-negative participants and 7 living with HIV) were included. Risk of vertical and horizontal HIV transmission and the effect of antiretroviral therapy on the fetus were the top considerations. However, individuals living with HIV prioritized vertical transmission, whereas HIV-negative participants prioritized horizontal transmission. Other factors of importance were probability of conception, stress of trying to conceive, cost associated with fertility clinics, and stigma associated with certain conception methods. This study builds our understanding of the preconception considerations for people living with HIV.

scholarly journals The Paradoxes of PrEP: Rejection, Reluctancy, and Novel Gay Identities in Biomedical HIV Prevention in Serbia

2022 ◽  
pp. 34-51
Author(s):  
Zoran Milosavljević
Keyword(s):  
Hiv Prevention ◽  
Gay Men ◽  
Hiv Transmission ◽  
Gay Identity ◽  
Hiv Status ◽  
Social Significance ◽  
Gay Communities ◽  
Hiv Status Disclosure ◽  
Status Disclosure ◽  
Hiv Negative

This article explores the different ways in which gay men in Serbia perceive PrEP as a novel method of HIV prevention. In the article, I draw on data from my research on PrEP use among thirty gay men in Belgrade. The use of PrEP is still very low amongst gay communities in Serbia due to their rejection of PrEP and due to the stigma around PrEP use. In Serbia, the social significance of PrEP relates to HIV status disclosure on gay social/dating media. Paradoxically, on gay dating sites, the signifier "PrEP" blurs the line between HIV positive gay men – who have achieved undetectable HIV status through a potent ARV therapy – and those HIV negative gay men who use PrEP as a preventative tool against HIV transmission. In the article, I will argue that a new form of gay identity has emerged on gay dating apps in Serbia – "undetectable, on PrEP." This new identity emerges from confusion in HIV risk assessment. The use of PrEP has been seen as a marker to denote someone’s HIV negative status and to protect them from HIV transmission. However, some gay men with an undetectable HIV status would like to be regarded as HIV negative even though they are not, and thus they use the signifier "on PrEP" to highlight their desire to claim an HIV negative status. PrEP has many symbolic valences: from HIV status disclosure to assumed promiscuity. As I will argue, while the health paradigm is of utmost importance for Serbian gay men, internalized stigma additionally drives the low uptake of PrEP amongst gay communities in Serbia, thus contributing to the confusion regarding PrEP use and the overall approach to HIV prevention. This article finds that those respondents who accept PrEP without stigma or confusion regarding their HIV status are also more willing and ready to recommend using PrEP to other gay men.

Sign in / Sign up

Export Citation Format

Share Document