Virus Production and Spontaneous Cell Proliferation in HTLV-I-Infected Lymphocytes

Mann, Dean L.; Martin, P J; Hamlin-Green, Gina; Nalewaik, R P; Blattner, William A.

doi:10.1006/clin.1994.1147

Cited by 23 publications

(17 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It appears that HTLV-1 infected T cells present antigens and costimulatory molecules on their cell surface that interact with CD8 + T cells to induce proliferation. Studies using blocking antibodies have shown that important pathways for spontaneous lymphocyte proliferation include IL-2 and IL-2 receptor,35,36 costimulatory molecules CD80 and CD86,37 adhesion molecules CD2/LFA-3 and possibly LFA-1/ICAM-1,34,35 and the class I HLA molecule 38. HTLV-1 infected B cells are not sufficient to stimulate lymphocyte proliferation,39 and the presence of adherent antigen presenting cells enhances proliferation 40.…”

Section: Discussionmentioning

confidence: 99%

Human T cell leukemia virus type 1 infection drives spontaneous proliferation of natural killer cells

et al. 2010

View full text Add to dashboard Cite

Most human T cell leukemia virus type 1 (HTLV-1) infected subjects remain asymptomatic throughout their lives, with a few individuals developing HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) or adult T cell leukemia. Lymphocytes from about half of HTLV-1 infected subjects spontaneously proliferate in vitro, and how this phenomenon relates to symptomatic disease outcome and viral burden is poorly understood. Spontaneous proliferation was measured in lymphocyte subsets, and these findings were correlated with HTLV-1 proviral load and Tax expression in PBMCs. We found that in addition to previously described vigorous CD8+ T cell spontaneous proliferation, natural killer (NK) cells spontaneously proliferated to a similar high level, resulting in expansion of CD56-expressing NK cells. Spontaneous NK cell proliferation positively correlated with HTLV-1 proviral load but not with Tax expression or the presence of HAM/TSP. The strongest correlate with clinical outcome in this cohort was the ability of cells to express Tax, while HTLV-1 proviral load was more closely related to spontaneous NK cell proliferation. These results demonstrate that spontaneous proliferation, Tax expression, and proviral load are inter-related but not equivalent, and that spontaneous lymphocyte proliferation is not restricted to T cells, the targets of HTLV-1 infection.

show abstract

Section: Discussionmentioning

confidence: 99%

Human T cell leukemia virus type 1 infection drives spontaneous proliferation of natural killer cells

et al. 2010

View full text Add to dashboard Cite

show abstract

“…A first milestone was the description of spontaneous incorporation of tritiated thymidine in peripheral blood mononuclear cells (PBMCs) cultivated in vitro (ex vivo) (12)(13)(14), indicating that lymphocytosis could result from increased rates of proliferation (13,15). The concept of this model has been counterbalanced by the discovery of mechanisms related to apoptosis.…”

mentioning

confidence: 99%

Increased cell proliferation, but not reduced cell death, induces lymphocytosis in bovine leukemia virus-infected sheep

Debacq

Asquith

Kerkhofs

et al. 2002

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

View full text Add to dashboard Cite

Lymphocyte homeostasis is the result of a critical balance between cell proliferation and death. Disruption of this subtle equilibrium can lead to the onset of leukemia, an increase in the number of lymphocytes being potentially due to both of these parameters. The relative importance of cell proliferation vs. apoptosis during pathogenesis induced by the primate T cell lymphotropic viruses and bovine leukemia virus (BLV) has been difficult to assess because of conflicting data from a range of in vitro and ex vivo experimental systems. Here, we aim to resolve this issue by measuring the rates of cell proliferation and death in the BLV-ovine system, an animal model of human T lymphotropic virus (HTLV-1). We use a method based on the i.v. injection of 5-bromodeoxyuridine into BLV-infected sheep. We show that B lymphocytes in BLV ؉ asymptomatic sheep proliferate significantly faster than in uninfected controls (average proliferation rate: 0.020 per day vs. 0.011 per day). In contrast, the rates of cell death were not significantly different between aleukemic BLV-infected and control sheep (average death rate 0.089 per day vs. 0.094 per day, respectively). We conclude that the increase in the number of B cells during BLVinduced lymphocytosis results from higher proliferation rates but is not due to a significant decrease in apoptosis, in contrast to data from in vitro (ex vivo) experiments. The imbalance created by the net increase in proliferation in the absence of compensating cell death reveals a complex mechanism of feedback regulation controlling homeostasis in the blood compartment.

show abstract

“…Interestingly, the results showed that blood mononuclear cells from HIV‐1/HTLV‐1 group, but not HIV‐1/HTLV‐2, have significant higher proliferative responses. While HTLV‐1 and HTLV‐2 have special tropism for infecting T‐cells and induce spontaneous lymphocyte proliferation [Itoyama et al, ; Prince et al, ; Mann et al, ], only HTLV‐1 has the ability to mediate diseases with severe prognosis (HAM/TSP and ATLL) with Tax1 playing a central role in the proliferation and transformation of HTLV‐1‐infected cells in vivo in ATLL [Marriott and Semmes, ]. Since individuals coinfected with HIV‐1/HTLV‐2 have been shown a less steep decline of CD4 + T‐cells [Beilke et al, ; Turci et al, ], this study also aimed to investigate whether the maintenance of mononuclear cell pool could be due to increased cell proliferation in this coinfected population.…”

Section: Discussionmentioning

confidence: 99%

High levels of CC-chemokine expression and downregulated levels of CCR5 during HIV-1/HTLV-1 and HIV-1/HTLV-2 coinfections

Barrios

Castillo

et al. 2015

J. Med. Virol.

View full text Add to dashboard Cite

The human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 are common copathogens among Human Immunodeficiency Virus (HIV)-infected individuals. HTLV-2 may confer a survival benefit among patients with HIV-1/HTLV-2 coinfections, along with lower plasma HIV-1 levels and delayed rates of CD4(+) T-cell decline. These effects have been attributed to the ability of the HTLV-2 viral transactivating Tax2 protein to induce the production of high levels of antiviral CC-chemokines and to downregulate expression of the CCR5 receptor, resulting in impaired entry of HIV-1 into CD4(+) T-cells. This study investigated the innate immunity of coinfected HIV/HTLV individuals by testing the ability of patient PBMCs to produce CC-chemokines in association CCR5 receptor modulation. The cellular proliferative responses of HIV/HTLV coinfected versus HIV monoinfected individuals were also evaluated. Higher levels of MIP-1α, MIP-1β, and RANTES (P < 0.05) were found in HIV-1/HTLV-2 coinfected group compared to HIV-1 monoinfected population. Upregulated levels of RANTES were shown in HIV-1/HTLV-1 after 1 and 3 days of culture (P < 0.05). Lymphocytes from HIV-1/HTLV-2 coinfected individuals showed significant CCR5 downregulation after 1 and 3 days of culture compared to lymphocytes from HIV-1 and uninfected groups (P < 0.05). Lower percentages of CCR5-positive cells were found in HIV-1/HTLV-1 coinfected after 3 days of incubation (P < 0.05). Levels of proliferation were significantly higher in the HIV-1/HTLV-1 group compared to HIV-1 alone (P < 0.05). HTLV-2 and HTLV-1 infections may induce the involvement of innate immunity against HIV-1 via stimulation of CC-chemokines and receptors, potentially modifying CCR5/HIV-1 binding and HIV-1 progression in coinfected individuals.

show abstract

Virus Production and Spontaneous Cell Proliferation in HTLV-I-Infected Lymphocytes

Cited by 23 publications

References 0 publications

Human T cell leukemia virus type 1 infection drives spontaneous proliferation of natural killer cells

Human T cell leukemia virus type 1 infection drives spontaneous proliferation of natural killer cells

Increased cell proliferation, but not reduced cell death, induces lymphocytosis in bovine leukemia virus-infected sheep

High levels of CC-chemokine expression and downregulated levels of CCR5 during HIV-1/HTLV-1 and HIV-1/HTLV-2 coinfections

Contact Info

Product

Resources

About