Percentage of CD3+CD4-CD8-γδTCR-T Cells Is Increased by HIV Disease

Mathiot, Nadine D.; Krueger, R.; French, Martyn; Price, Patricia

doi:10.1089/088922201750290096

Cited by 19 publications

(15 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…37 Our finding that previously immunodeficient HIV patients with variable T cell recovery on ART all have normal numbers of ␥␦ T cells would support this. 39 Previous studies have shown an inverse relationship between circulating IL-7 levels and CD4 ϩ T cell counts, 16 as well as markers of thymic function. 17 However, we observed no correlation between serum IL-7 levels and total CD4 ϩ T cell counts, naive T cell counts, TREC concentrations, or thymic volume.…”

Section: Discussionmentioning

confidence: 97%

Thymic Function in Severely Immunodeficient HIV Type 1-Infected Patients Receiving Stable and Effective Antiretroviral Therapy

Fernández

Nolan

Price

et al. 2006

AIDS Research and Human Retroviruses

Self Cite

View full text Add to dashboard Cite

The role of the thymus in long-term immune reconstitution has not been addressed in HIV patients who were severely immunodeficient prior to successful treatment with combination antiretroviral therapy (ART). Adult HIV-1 patients (n = 78) with nadir CD4+ T cell counts <100 T cells/microl, at least 12 months on ART and 6 months of complete viral suppression (<50 HIV RNA copies/ml) were selected from a patient database. The cohort was divided according to current CD4+ T cell counts and patients from the lowest (n = 15) and highest (n = 12) tertiles were studied. Thymic volume was assessed by spiral computed tomography. Naive (CD45RA+CD62L+) and replicating (Ki67+) T cells were quantitated by flow cytometry, T cell receptor excision circles (TREC) were assessed by real-time PCR, and serum IL-7 and testosterone by immunoassay. Patients with low CD4+ T cell counts had smaller thymuses [0(0-5.3) vs. 3.5(0-15.6) cm(3), p = 0.04] and were more likely to have no detectable thymus. They had similar proportions of replicating cells, but fewer naive CD4+ and CD8+ T cells and less TREC in CD4+ and CD8+ T cells/ml of blood than patients with high CD4+ T cell counts. However, some patients with no detectable thymus had high numbers of naive and TREC-bearing T cells. Thus, the recovery of CD4+ T cells in severely immunodeficient HIV patients with a virological response to ART is probably limited by thymic function. However, the data are consistent with extrathymic T cell production contributing to the naive T cell pool in some patients.

show abstract

Section: Discussionmentioning

confidence: 97%

Thymic Function in Severely Immunodeficient HIV Type 1-Infected Patients Receiving Stable and Effective Antiretroviral Therapy

Fernández

Nolan

Price

et al. 2006

AIDS Research and Human Retroviruses

Self Cite

View full text Add to dashboard Cite

show abstract

“…CD4 ϩ and CD8 ϩ T cells were isolated using CD4 or CD8 MicroBeads, respectively. Double-negative T cells positive for ␣␤ TCR were enriched by magnetic depletion using a cocktail of biotin-conjugated antibodies against CD8, CD14, CD16, CD19, CD36, CD56, CD123, ␥/␦ TCR, and CD235a subsequently linked to streptavidin-coupled paramagnetic beads (CD4 ϩ T-cell Ϫ /CD8 Ϫ T cells was assumed to be approximately 50% (43).…”

Section: Methodsmentioning

confidence: 99%

Productive Human Immunodeficiency Virus Type 1 Infection in Peripheral Blood Predominantly Takes Place in CD4/CD8 Double-Negative T Lymphocytes

Kaiser

Joos

Niederöst

et al. 2007

J Virol

108

View full text Add to dashboard Cite

“…Ϫ fraction has been reported to be 5% and to be unaltered by HIV infection, CD4 count, or antiretroviral therapy (11).…”

Section: Cd4mentioning

confidence: 99%

Dynamics of T Cells and TCR Excision Circles Differ After Treatment of Acute and Chronic HIV Infection

Lewin

Ribeiro

Kaufmann

et al. 2002

The Journal of Immunology

View full text Add to dashboard Cite

We quantified T cell proliferation and thymic function in primary HIV infection (PHI; n ‫؍‬ 19) and chronic HIV infection (CHI;n H uman immunodeficiency virus type 1 infection is marked by a progressive loss of CD4ϩ T cells, eventually leading to immunodeficiency and death. The pathogenesis of T cell depletion in HIV infection is complex, and debate continues as to whether T cell depletion is predominantly caused by increased T cell death, enhanced T cell proliferation and subsequent "exhaustion," or an inhibition of de novo T cell production (reviewed in Ref. 1). After effective antiretroviral therapy, this process is reversed in the majority of individuals and there is an increase in both CD4 ϩ naive and memory T cells and partial reconstruction of functional immunity (2).The role of the thymus in T cell homeostasis is critical to our understanding of T cell depletion, T cell turnover, and immune reconstitution. A fraction of recent thymic emigrants carries episomal TCR excision circles (TREC) 5 that do not replicate with cell division (3, 4). The number of TREC per million cells is dependent on thymic output, T cell proliferation, and the rate of death of both TREC-positive and -negative T cells. Hazenberg et al. (5) demonstrated an inverse relationship between the number of TREC per million cells and cell division in the naive T cell population from individuals with chronic HIV infection (CHI), suggesting that the reduction of TREC per million cells in HIV infection is a consequence of increased T cell proliferation and is not due to a reduction in thymic output. As suggested by Hazenberg et al. (5), interpretation of these results is complex because T cell proliferation, T cell death, and thymic function are all altered by HIV infection (6 -8) and, in addition, each of these processes will also affect the quantification of TREC (4, 9).To help unravel these competing processes we quantified TREC in two ways. First, we measured TREC per million T cells (CD4 ϩ and CD4 Ϫ ) and then, to account for changes in T cell number due to either HIV infection or therapy, we calculated TREC per milliliter of blood. Proliferation, for example, is thought to decrease TREC by dilution (5). This is clearly true if one measures TREC per million CD4 ϩ T cells, because division will not increase the number of TREC but will increase the number of cells. However, if one measures TREC per milliliter there will be no change because the number of TREC remains unchanged during cell division. If death occurs simultaneously with proliferation to maintain cell numbers, then TREC per milliliter will decrease as TREC ϩ

show abstract

Percentage of CD3⁺CD4^-CD8^-γδTCR^-T Cells Is Increased by HIV Disease

Cited by 19 publications

References 17 publications

Thymic Function in Severely Immunodeficient HIV Type 1-Infected Patients Receiving Stable and Effective Antiretroviral Therapy

Thymic Function in Severely Immunodeficient HIV Type 1-Infected Patients Receiving Stable and Effective Antiretroviral Therapy

Productive Human Immunodeficiency Virus Type 1 Infection in Peripheral Blood Predominantly Takes Place in CD4/CD8 Double-Negative T Lymphocytes

Dynamics of T Cells and TCR Excision Circles Differ After Treatment of Acute and Chronic HIV Infection

Contact Info

Product

Resources

About