Surface immunoglobulin-positive T lymphocytes in HIV-1 infection: Relationship to CD4+ lymphocyte depletion

Ardman, Blair; Mayer, Kenneth H.; Bristol, J. Andrew; Ryan, Mark; Settles, Michael; Levy, Elinor M.

doi:10.1016/0090-1229(90)90146-h

Cited by 12 publications

(8 citation statements)

References 18 publications

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“…Previous studies in SIV and HIV have shown inverse correlations between plasma or serum autoantibody levels and peripheral CD4 + T cell counts, suggesting that autoantibodies against surface antigens on CD4 + T cells may play a role in CD4 + T cell decline [16][17][18][19]. However, these studies only investigated autoantibodies of diverse surface proteins on CD4 + T cells in untreated HIV patients or animal models.…”

Section: Discussionmentioning

confidence: 99%

The effect of plasma auto-IgGs on CD4+ T cell apoptosis and recovery in HIV-infected patients under antiretroviral therapy

Luo

Zhou

Ogunrinde

et al. 2017

Journal of Leukocyte Biology

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Although effective antiretroviral therapy (ART) suppresses HIV viral replication, prevents AIDS-related complications, and prolongs life, a proportion of patients fails to restore the patients' CD4 T cell number to the level of healthy individuals. Increased mortality and morbidity have been observed in these patients. In the current study, we have investigated the role of auto-IgGs in CD4 T cell apoptosis and recovery in a cross-sectional study. All HIV subjects were on viral-suppressive ART treatment with a different degree of CD4 T cell reconstitution. Total auto-IgG binding on CD4 T cell surfaces and its associated apoptosis and CD4 T cell recovery were analyzed by flow cytometry ex vivo. Total IgGs from plasma were tested for their binding capacities to CD4 T cell surfaces and their mediation to CD4 T cell death through NK cell cytotoxicity in vitro. HIV subjects had increased surface binding of auto-IgGs on CD4 T cells compared with healthy controls, and IgG binding was associated with elevated CD4 T cell apoptosis in HIV subjects but not in healthy controls. Plasma IgGs from HIV subjects bound to CD4 T cells and induced cell apoptosis through NK cytotoxicity in vitro. Soluble CD4 (sCD4) preincubation prevented NK cell-mediated CD4 T cell death. Our results suggest that plasma autoantibodies may play a role in some HIV patients with poor CD4 T cell recovery under viral-suppressive ART.

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Section: Discussionmentioning

confidence: 99%

The effect of plasma auto-IgGs on CD4+ T cell apoptosis and recovery in HIV-infected patients under antiretroviral therapy

Luo

Zhou

Ogunrinde

et al. 2017

Journal of Leukocyte Biology

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“…Additionally, although the presence of these antibodies is not at issue, it has been difficult to clearly show cause and effect. Several studies have shown an association between anti-CD4 + T cell antibodies with CD4 T + cell depletion and disease progression [40], [47]–[49], suggesting the potential contribution to AIDS pathogenesis. However, none of these studies have clearly identified the mechanism within, and the subset in CD4 + T cells that is depleted.…”

Section: Discussionmentioning

confidence: 99%

Association of Progressive CD4+ T Cell Decline in SIV Infection with the Induction of Autoreactive Antibodies

et al. 2009

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The progressive decline of CD4+ T cells is a hallmark of disease progression in human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infection. Whereas the acute phase of the infection is dominated by virus-mediated depletion of memory CD4+ T cells, chronic infection is often associated with a progressive decline of total CD4+ T cells, including the naïve subset. The mechanism of this second phase of CD4+ T cell loss is unclear and may include immune activation–induced cell death, immune-mediated destruction, and regenerative or homeostatic failure. We studied patterns of CD4+ T cell subset depletion in blood and tissues in a group of 20 rhesus macaques inoculated with derivatives of the pathogenic SIVsmE543-3 or SIVmac239. Phenotypic analysis of CD4+ T cells demonstrated two patterns of CD4+ T cell depletion, primarily affecting either naïve or memory CD4+ T cells. Progressive decline of total CD4+ T cells was observed only in macaques with naïve CD4+ T cell depletion (ND), though the depletion of memory CD4+ T cells was profound in macaques with memory CD4+ T cell depletion (MD). ND macaques exhibited lower viral load and higher SIV-specific antibody responses and greater B cell activation than MD macaques. Depletion of naïve CD4+ T cells was associated with plasma antibodies autoreactive with CD4+ T cells, increasing numbers of IgG-coated CD4+ T cells, and increased incidence of autoreactive antibodies to platelets (GPIIIa), dsDNA, and phospholipid (aPL). Consistent with a biological role of these antibodies, these latter antibodies were accompanied by clinical features associated with autoimmune disorders, thrombocytopenia, and catastrophic thrombotic events. More importantly for AIDS pathogenesis, the level of autoreactive antibodies significantly correlated with the extent of naïve CD4+ T cell depletion. These results suggest an important role of autoreactive antibodies in the CD4+ T cell decline observed during progression to AIDS.

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“…have shown that HIVinfected patients without anti-lymphocyte antibodies seem not to progress to AIDS [30]. Moreover, an association of anti-CD4 cell antibodies with CD4 cell depletion has been demonstrated in recent studies [31,32]. In contrast, other studies did not show evidence for an association between anti-lymphocyte antibodies and CD4 eell depletion [11,24].…”

Section: Discussionmentioning

confidence: 88%

Anti-lymphocyte antibodies in plasma of HIV-1–infected patients preferentially react with MHC class Il-negative T cells and are linked to antibodies against gp41

Müller

Kukel

Schneweis

et al. 1994

Clinical and Experimental Immunology

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SUMMARYIt has previously beeti shown that HIV-infected patients develop anti-lymphocyte antibodies. The relationship between anti-lymphocyte antibodies and antibodies against different viral antigens is unknown, and it remains controversial whether some lymphocyte subpopulations are targeted preferentially. We have set out using three-colour flow cytometry to measure antibodies against different lymphocyte subsets. Staining with anti-human immunoglobulin and two MoAbs was performed to characterize the immunoglobulin toad of different lymphocyte subsets. Comparison was done between patients' antibody reactivity against HlV-1 antigens and anti-lymphocyte antibodies. We were able to demonstrate the presence of anti-lymphocyte antibodies in approximately 75% of the HIV-infected patients (n = 78) (healthy controls were all negative). MHC class Il-negative T cells showed a stronger reaction wilh anti-lymphocyte antibodies than B eells or MHC class Il-positive T cells. Patients wilh antibodies against CD4 lymphocytes showed a signilicantly higher antibody reaction with the retroviral antigen gp41 than patients without these antibodies. An association between anti-lymphocyte antibodies and antibody reactivity against other HIV-1 antigens was not noticed. In conclusion, anti-lymphocyte antibodies in HIV-Iinfecled patients show a preferential reaetivitiy with T eells which lack expression of MHC class II molecules. There is an increased antibody reactivity against gp41 in patients with anti-CD4* Teell antibodies. The association hints at a specific origin of anti-lymphocyte antibodies in HIV-Iinfected patients due to cross-reactivity with viral epitopes or network phenomena. These anti-CD4 eell antibodies eould be of interest in the elinical course of HIV infection.

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Surface immunoglobulin-positive T lymphocytes in HIV-1 infection: Relationship to CD4+ lymphocyte depletion

Cited by 12 publications

References 18 publications

The effect of plasma auto-IgGs on CD4+ T cell apoptosis and recovery in HIV-infected patients under antiretroviral therapy

The effect of plasma auto-IgGs on CD4+ T cell apoptosis and recovery in HIV-infected patients under antiretroviral therapy

Association of Progressive CD4+ T Cell Decline in SIV Infection with the Induction of Autoreactive Antibodies

Anti-lymphocyte antibodies in plasma of HIV-1–infected patients preferentially react with MHC class Il-negative T cells and are linked to antibodies against gp41

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