Changes in CD4+ T-Cell Differentiation Phenotype During Structured Treatment Interruption in Patients With Chronic HIV-1 Infection

Alexander, Thomas; Ortiz, Gabriel M.; Wellons, Melissa; Allen, Andrew S.; Grace, Edward J.; Schweighardt, Becky; Brancato, Jason; Sandberg, Johan K.; Furlan, Scott N.; Miralles, G. Diego; Nixon, Douglas F.; Bartlett, John A.

doi:10.1097/00126334-200312150-00005

Cited by 21 publications

(17 citation statements)

References 31 publications

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“…2A). This profile of CD4 ϩ cell subpopulation distribution did not differ from those previously reported for a healthy donor population (respectively, 28, 58, 12, and 2%) (31). We found that Cy-G-CSF treatment induced a slight but significant ( p Ͻ 0.05) decrease in naive CD4 ϩ cells relative rate (from 28 to 19%), whereas the percentages of the three subpopulations of memory CD4 ϩ cell (central memory, effector memory, and late effector) were not significantly affected ( Fig.…”

Section: Mobilization Of Naive Central Memory Effector Memory and supporting

confidence: 62%

Functional Regulatory T Cells Are Collected in Stem Cell Autografts by Mobilization with High-Dose Cyclophosphamide and Granulocyte Colony-Stimulating Factor

Condomines

Quittet

Lu³

et al. 2006

The Journal of Immunology

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High-dose cyclophosphamide (Cy) and G-CSF are widely used to mobilize hemopoietic stem cells for treating patients with high-dose chemotherapy and autologous stem cell transplantation (ASCT). Because lymphocyte count in the graft collected after Cy-G-CSF treatment is an independent survival factor after ASCT for patients with multiple myeloma, our purpose was to study how Cy-G-CSF treatment affects the phenotype and function of T cells in patients with multiple myeloma. Cy induced a 3-fold decrease of T cell counts with a slow and partial T cell recovery of one-third at the time of hemopoietic stem cell collection. Cy-G-CSF treatment did not affect the relative ratios of central memory, effector memory, and late effector CD4+ or CD8+ T cells, but a decrease in the percentage of naive CD4+ cells was observed. The percentages of CD25+ cells increased 2- to 3-fold in CD4+ and CD8+ T cells, the former including both activated CD25low and CD25high cells. CD4+CD25high cells were regulatory T cells (Treg) that expressed high levels of FOXP3, CTLA-4, and GITR and displayed in vitro suppressive properties. The recovery of Treg absolute counts after Cy-G-CSF treatment was higher than the recovery of other lymphocyte subpopulations. In conclusion, Cy-G-CSF treatment induces a severe T cell count decrease without deleting Treg, which are potent inhibitors of antitumor response. The present data encourage novel therapeutic strategies to improve T cell recovery following ASCT while limiting Treg expansion.

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Section: Mobilization Of Naive Central Memory Effector Memory and supporting

confidence: 62%

Functional Regulatory T Cells Are Collected in Stem Cell Autografts by Mobilization with High-Dose Cyclophosphamide and Granulocyte Colony-Stimulating Factor

Condomines

Quittet

Lu³

et al. 2006

The Journal of Immunology

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“…This rapid decline and rebound are consistent with previous observations on CD4 T-cell redistribution (13,14) and the conclusion that very short therapy interruptions in subjects with preserved CD4 counts do not have the ongoing detrimental immunologic impact seen with longer treatment interruptions. The safety of brief STI is supported by several other studies (26)(27)(28) showing that brief STIs do not affect overall CD4 T-cell count and importantly, do not diminish immune function as determined by antigen recall responses.…”

Section: Discussionmentioning

confidence: 64%

Large number of rebounding/founder HIV variants emerge from multifocal infection in lymphatic tissues after treatment interruption

Rothenberger

Keele

Wietgrefe

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

240

213

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Antiretroviral therapy (ART) suppresses HIV replication in most individuals but cannot eradicate latently infected cells established before ART was initiated. Thus, infection rebounds when treatment is interrupted by reactivation of virus production from this reservoir. Currently, one or a few latently infected resting memory CD4 T cells are thought be the principal source of recrudescent infection, but this estimate is based on peripheral blood rather than lymphoid tissues (LTs), the principal sites of virus production and persistence before initiating ART. We, therefore, examined lymph node (LN) and gut-associated lymphoid tissue (GALT) biopsies from fully suppressed subjects, interrupted therapy, monitored plasma viral load (pVL), and repeated biopsies on 12 individuals as soon as pVL became detectable. Isolated HIV RNA-positive (vRNA+) cells were detected by in situ hybridization in LTs obtained before interruption in several patients. After interruption, multiple foci of vRNA+ cells were detected in 6 of 12 individuals as soon as pVL was measureable and in some subjects, in more than one anatomic site. Minimal estimates of the number of rebounding/founder (R/F) variants were determined by single-gene amplification and sequencing of viral RNA or DNA from peripheral blood mononuclear cells and plasma obtained at or just before viral recrudescence. Sequence analysis revealed a large number of R/F viruses representing recrudescent viremia from multiple sources. Together, these findings are consistent with the origins of recrudescent infection by reactivation from many latently infected cells at multiple sites. The inferred large pool of cells and sites to rekindle recrudescent infection highlights the challenges in eradicating HIV.

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“…ϩ lymphocytes, such expression patterns have been previously described for eight healthy controls in the United States (1). In that study, 28% Ϯ 2% (mean Ϯ standard error of the mean) of CD4 ϩ T cells were T naïve (CD45RA ϩ CCR7 ϩ ), 59% Ϯ 2% were T CM (CD45RA Ϫ CCR7 ϩ ), 11% Ϯ 1% were T EM (CD45RA Ϫ CCR7 Ϫ ), and 2% Ϯ 1% were T EMRA (CD45RA ϩ CCR7 Ϫ ).…”

Section: Cd56mentioning

confidence: 88%

“…Ϫ CD4 ϩ T cells-a population which is very small in healthy individuals and has not been well characterized (1,11). Data on the frequencies and absolute numbers of these T-cell subpopulations are not available for populations in subSaharan Africa.…”

mentioning

confidence: 99%

Evaluation of a Simplified Dual-Platform Flow Cytometric Method for Measurement of Lymphocyte Subsets and T-Cell Maturation Phenotypes in the Population of Nouna, Burkina Faso

Böhler

Klose

et al. 2007

Clin Vaccine Immunol

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In the context of a larger clinical study in Nouna, Burkina Faso, we evaluated a simplified dual-platform (DP) flow cytometric (FCM) method that allows the determination of major lymphocyte subsets in a single test tube. We compared the phenotyping of lymphocytes with DP FCM and simultaneous measurements with standard single-platform (SP) FCM for samples from 177 individuals. Analysis of the comparative measurements revealed that DP FCM systematically underestimates the proportion of NK cells, overestimates the percentage of CD3 ؉ CD8 ؉ lymphocytes, and yields proportions of B cells and CD4 ؉ T cells comparable with the results from SP FCM. Bland-Altman analysis showed a low bias between both methods and an acceptable precision for percent values of CD4 ؉ T cells (bias ؎ precision, ؊1% ؎ 6%) and CD8 ؉ T cells (؊3% ؎ 6%). The absolute cell numbers of all lymphocyte subpopulations, however, were systematically biased towards lower values being obtained by DP FCM. Reference values for the distribution of T-cell maturation phenotypes in 177 healthy adults were calculated using DP FCM. The mean ؎ standard deviation (SD) CD4؉ -to-CD8 ؉ T-cell ratio was 1.61 ؎ 0.61, the mean percentage ؎ SD of CD4 ؉ T cells was 42% ؎ 7%, and that of CD8 ؉ T cells 29% ؎ 7%. Among CD4 ؉ lymphocytes, 28% ؎ 7% were classified as central memory (CD45RA low CCR7 ؉ ), 22% ؎ 10% as naïve (CD45RA high CCR7 ؉ ), 45% ؎ 12% as effector memory (CD45RA low CCR7 ؊ ); and 5% ؎ 3% as terminally differentiated effector memory expressing CD45RA (CD45RA high CCR7 ؊ ). Among CD8 bright lymphocytes, 3% ؎ 2% had a central memory phenotype, 27% ؎ 13% were naïve, 37% ؎ 13% had an effector memory phenotype, and 34% ؎ 12% were terminally differentiated effector memory cells expressing CD45RA.In the years 2004 and 2005, a population-based study was performed in Nouna, Burkina Faso, in order to generate site-and gender-specific reference values for lymphocyte subsets in healthy adults in the context of an expanding program for prevention of mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) (17). During that study, single-platform (SP) flow cytometry (FCM) was used (9), a method which is not available to most laboratories in developing countries due to its relatively high cost (7).Since lymphocyte differentiation and counting by FCM is needed for immunological monitoring of antiretroviral treatment in resource-limited settings and immunological field studies on cohorts of young infants suffering from diseases other than infection with HIV-1 were planned in our research setting, we wanted to use an FCM test which allows the determination of the complete lymphocyte differential. The test should be reliably performed with low volumes of venous and capillary blood and should be resistant against preanalytic errors. It should be as inexpensive as possible and should be run on a simple flow cytometer equipped with only one laser.In the present study, we evaluated such a simplified dualplatform (DP) FCM method for its clinical use in Nouna. The m...

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Changes in CD4+ T-Cell Differentiation Phenotype During Structured Treatment Interruption in Patients With Chronic HIV-1 Infection

Cited by 21 publications

References 31 publications

Functional Regulatory T Cells Are Collected in Stem Cell Autografts by Mobilization with High-Dose Cyclophosphamide and Granulocyte Colony-Stimulating Factor

Functional Regulatory T Cells Are Collected in Stem Cell Autografts by Mobilization with High-Dose Cyclophosphamide and Granulocyte Colony-Stimulating Factor

Large number of rebounding/founder HIV variants emerge from multifocal infection in lymphatic tissues after treatment interruption

Evaluation of a Simplified Dual-Platform Flow Cytometric Method for Measurement of Lymphocyte Subsets and T-Cell Maturation Phenotypes in the Population of Nouna, Burkina Faso

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