Feline CD8+ T cell non-cytolytic anti-feline immunodeficiency virus activity mediated by a soluble factor(s).

Hohdatsu, Tsutomu; Okubo, Michihito; Koyama, Hiroyuki

doi:10.1099/0022-1317-79-11-2729

Cited by 20 publications

(15 citation statements)

References 19 publications

(22 reference statements)

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“…However, these factors and CTL alone cannot explain all of the suppression mechanisms and unidentified factors, including the CD8 ϩ cell antiviral factor (CAF), have been considered to exist (15,16,23,24). As in HIV infection, the anti-FIV activity of CD8 ϩ T cells with non-CTL characteristics has been observed in FIV-infected cats (4,7,11,13). There are two possible causes in the decrease of CD4 ϩ T cells due to FIV infection.…”

Section: Discussionmentioning

confidence: 99%

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Ability of CD8⁺ T Cell Anti‐Feline Immunodeficiency Virus Activity Correlated with Peripheral CD4⁺ T Cell Counts and Plasma Viremia

Hohdatsu

Yamazaki

Yamada

et al. 2003

Microbiology and Immunology

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In the host defense mechanism against feline immunodeficiency virus (FIV) infection, CD8+ T cells specifically attack virus‐infected cells and suppress the replication of the virus in a non‐cytolytic manner by secreting soluble factors. In this study, we measured CD8+ T cell anti‐FIV activity in 30 FIV‐infected cats. We investigated its relationship with the number of peripheral blood lymphocytes, particularly the CD4+ T cell and CD8+ T cell counts, and the relationship between anti‐FIV activity and the number of T cells of CD8α+βlo and CD8α+β− phenotypes. A clearly significant correlation was observed between anti‐FIV activity and the number of CD4+ T cells. A weaker anti‐FIV activity was associated with a greater decrease in the number of CD4+ T cells. However, there was no significant correlation between anti‐FIV activity and the number of B or CD8+ T cells. Compared with SPF cats, FIV‐infected cats had significantly higher CD8α+βlo T cell and CD8α+β− T cell counts, but, no significant correlation was observed between these cell counts and anti‐FIV activity. This anti‐FIV activity significantly correlated with plasma viremia, which was detected in cats with a weak anti‐FIV activity. These results suggest that the anti‐FIV activity of CD8+ T cells plays an important role in plasma viremia and the maintenance of CD4+ T cells in the body. It is unlikely that CD8α+βlo or CD8α+β− T cells appearing after FIV infection represent a phenotype of CD8+ cells with anti‐FIV activity.

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Section: Discussionmentioning

confidence: 99%

“…؉ T cell counts, and the relationship between anti-FIV activity and the number of T cells of CD8␣ soluble factors, have been observed in the AP and AC stages of FIV infection (4,7,11,13). Cell-mediated immune responses chiefly involving these CD8 ϩ T cells appear to maintain the AC stage of FIV infection.…”

Section: T Cell and Cd8mentioning

confidence: 99%

Ability of CD8⁺ T Cell Anti‐Feline Immunodeficiency Virus Activity Correlated with Peripheral CD4⁺ T Cell Counts and Plasma Viremia

Hohdatsu

Yamazaki

Yamada

et al. 2003

Microbiology and Immunology

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“…These cells suppress virus replication in CD4 + T cells in a non-cytotoxic, non-MHC restricted manner by either a contact-dependent (Bucci et al, 1998a;Gebhard et al, 1999) or -independent mechanism Hohdatsu et al, 1998;Choi et al, 2000). Bucci et al (1998a) detected non-cytotoxic, contact-dependent anti-viral CD8 + cell activity at 6 weeks p.i.…”

Section: Cell-mediated Immune Responsementioning

confidence: 99%

“…FIV infection results in an increase in circulating CD8 + T cells that occurs early after infection and is sustained throughout the asymptomatic phase of infection, only to decline as the cat develops AIDS-like disease (Ackley et al, 1990;Tompkins et al, 1991;English et al, 1994).The increase in CD8 + T cell numbers is associated with the development of CD8 + antiviral activity through both cytotoxic (Song et al, 1992;Song et al, 1995;Beatty et al, 1996;Burkhard et al, 2001;Flynn et al, 2002) and non-cytotoxic mechanisms (Bucci et al, 1998a;Hohdatsu et al, 1998;Gebhard et al, 1999;Choi et al, 2000;Flynn et al, 2002) and has been linked to a decline in plasma viremia (Bucci et al, 1998a;Hohdatsu et al, 2003). Beatty et al (1996) detected anti-FIV Gag-specific CD8 + cytotoxic activity in peripheral blood as early as 2 weeks post infection, and the activity remained high through the acute phase infection, up to 21 weeks post infection (p.i.).…”

Section: Cell-mediated Immune Responsementioning

confidence: 99%

Lentivirus-induced immune dysregulation

Tompkins

2008

Veterinary Immunology and Immunopathology

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FIV/HIV infections are associated with an early robust humoral and cellular anti-viral immune response followed by a progressive immune suppression that eventually results in AIDS. Several mechanisms responsible for this immune dysfunction have been proposed including cytokine dysregulation, immunologic anergy and apoptosis, and inappropriate activation of immune regulatory cells. Studies on FIV infection provide evidence for all three. Cytokine alterations include decreases in IL2 and IL12 production and increases in IFNγ and IL10 in FIV + cats compared to normal cats. The elevated IL10:IL12 ratio is associated with the inability of FIV + cats to mount a successful immune response to secondary pathogens. Additionally, chronic antigenic (FIV) stimulation results in an increase in the percent of activated T cells expressing B7 and CTLA4 costimulatory molecules in infected cats. The expression of these molecules is associated with T cells that are undergoing apoptosis in the lymph nodes. As ligation of CTLA4 by B7 transduces a signal for induction of anergy, one can speculate that the activated T cells are capable of T cell-T cell interactions resulting in anergy and apoptosis. The inability of CD4 + cells from FIV + cats to produce IL2 in response to recall antigens and the gradual loss of CD4 + cell numbers could be due to B7-CTLA4 interactions. The chronic antigenemia may also lead to activation of CD4 + CD25 + T regulatory cells. Treg cells from FIV + cats are chronically activated and inhibit the mitogen-induced proliferative response of CD4 + CD25 − by down-regulating IL2 production. Although Treg cell activation can be antigen specific, the suppressor function is not, and thus activated Treg cells would suppress responses to secondary pathogens as well as to FIV. Concomitant with the well known virus-induced immune suppression is a progressive immune hyper-activation. Evidence for immune hyper-activation includes polyclonal B cell responses, gradual replacement of naïve CD4 + and CD8 + T cell phenotypes with activation phenotypes (CD62L − , B7 + , CTLA4 + ), and the chronic activation of CD4 + CD25 + Treg cells. Thus lentivirus infections lead to severe immune dysregulation manifested as both chronic immune suppression and chronic immune activation. FIV infection of cats provides a number of advantages over other lentivirus infections as a model to study this immune dysregulation. It is a natural infection that has existed in balance with the cat's immune system for thousands of years. As such, the natural history and pathogenesis provides an excellent model to study the long term relationships between AIDS lentivirus and host immune system function/ dysregulation.

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“…Following infection with FIV the host mounts a vigorous virus-speci®c cytotoxic T cell (CTL) response which precedes the development of virus-speci®c humoral immunity (Song et al, 1992;Beatty et al, 1996). In addition, non-cytolytic CD8 T cells, which suppress virus replication in a non-MHC-restricted manner by the secretion of soluble factors, have been described during acute and asymptomatic stages of FIV infection (Jeng et al, 1996;Hohdatsu et al, 1998;Veterinary Immunology and Immunopathology 85 (2002) 159±170 Flynn et al, 1999;Choi et al, 2000). Studies aimed at elucidating the immune correlates of vaccinal immunity have revealed that virus neutralising antibodies, virus-speci®c CTLs, and CD8 T cells capable of suppressing FIV replication, are all involved, either acting alone or in concert (Flynn et al, , 1999Hosie and Flynn, 1996).…”

Section: Introductionmentioning

confidence: 99%

Involvement of cytolytic and non-cytolytic T cells in the control of feline immunodeficiency virus infection

Flynn

Dunham

Mueller

et al. 2002

Veterinary Immunology and Immunopathology

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The appearance of non-cytolytic T cells that suppressed feline immunode®ciency virus (FIV) replication in vitro, and FIV-speci®c cytotoxic T cell (CTL) responses was compared in a group of seven, speci®c pathogen free (SPF) domestic cats following primary infection with the Glasgow 8 isolate of FIV (FIV ). FIV proviral burdens were quanti®ed in the blood and lymphoid tissues by real-time PCR. Non-cytolytic T cell suppression of FIV replication was measured by co-cultivating lymphoblasts prepared from the cats at different time-points during infection with FIV-infected MYA-1 cells in vitro. Non-cytolytic suppressor activity was detected as early as 1 week after infection, and was evident in all the lymphoid tissues examined. Further, this activity was present in subpopulations of T cells in the blood with normal (CD8 hi ) or reduced (CD8 lo ) expression of the CD8 molecule, and temporal modulations in non-cytolytic suppressor activity were unrelated to the circulating CD8 T cell numbers. Virus-speci®c CTL responses, measured by 51 Cr release assays, were not detected until 4 weeks after infection, with the emergence of FIV-speci®c effector CTLs in the blood. Throughout infection the response was predominantly directed towards FIV Gag-expressing target cells, and by 47 weeks after infection CTL responses had become localised in the lymph nodes and spleen. The results suggest that both non-cytolytic T cell suppression of FIV replication and FIV-speci®c CTL responses are important cellular immune mechanisms in the control of FIV replication in infected asymptomatic cats. #

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Feline CD8+ T cell non-cytolytic anti-feline immunodeficiency virus activity mediated by a soluble factor(s).

Cited by 20 publications

References 19 publications

Ability of CD8⁺ T Cell Anti‐Feline Immunodeficiency Virus Activity Correlated with Peripheral CD4⁺ T Cell Counts and Plasma Viremia

Ability of CD8⁺ T Cell Anti‐Feline Immunodeficiency Virus Activity Correlated with Peripheral CD4⁺ T Cell Counts and Plasma Viremia

Lentivirus-induced immune dysregulation

Involvement of cytolytic and non-cytolytic T cells in the control of feline immunodeficiency virus infection

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Feline CD8+ T cell non-cytolytic anti-feline immunodeficiency virus activity mediated by a soluble factor(s).

Cited by 20 publications

References 19 publications

Ability of CD8+ T Cell Anti‐Feline Immunodeficiency Virus Activity Correlated with Peripheral CD4+ T Cell Counts and Plasma Viremia

Ability of CD8+ T Cell Anti‐Feline Immunodeficiency Virus Activity Correlated with Peripheral CD4+ T Cell Counts and Plasma Viremia

Lentivirus-induced immune dysregulation

Involvement of cytolytic and non-cytolytic T cells in the control of feline immunodeficiency virus infection

Contact Info

Product

Resources

About

Ability of CD8⁺ T Cell Anti‐Feline Immunodeficiency Virus Activity Correlated with Peripheral CD4⁺ T Cell Counts and Plasma Viremia

Ability of CD8⁺ T Cell Anti‐Feline Immunodeficiency Virus Activity Correlated with Peripheral CD4⁺ T Cell Counts and Plasma Viremia