T-cell responses to human immunodeficiency virus (HIV) and its recombinant antigens in HIV-infected chimpanzees

Eichberg, J. W.; Zarling, Joyce M.; Alter, H. J.; Levy, Jay A.; Berman, P W; Gregory, Timothy J.; Lasky, Laurence A.; McClure, Jan; Cobb, Kathy; Morán, Patricia

doi:10.1128/jvi.61.12.3804-3808.1987

Cited by 60 publications

(19 citation statements)

References 19 publications

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“…T helper-cell responses against gpI20 have been demonstrated in individuals exposed repeatedly to HIV-1 but lacking serological or other evidence of HIV-1 infection [5]. Furthermore, HIV-1 infected apes, which do not seem to develop HIV-1-reiated disease, have vigorous T helper-cell responses towards various HIV-1 antigens [6,7].…”

Section: Introductionmentioning

confidence: 99%

Kinetics and Specificities of the T Helper–Cell Response to GP120 in the Asymptomatic Stage of HIV–1 Infection

Geretti¹,

Baalen²,

Borleffs³

et al. 1994

Scand J Immunol

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Geretti AM, Van Baalen CA, Borleffs JCC, van Els CACM, Osterhaus ADME. Kinetics and Specificities ofthe T Helper-Cell Response togpl20 in the Asymptomatic Stage of HIV-1 Infection. Scand J Immunol 1994:39:355-62 Peripheral blood mononuclear cells from 36 asymptomatic HIV-1 seropositive individuals were tested longitudinally for in vitro T-cell proliferation and IL-2 production in response to synthetic peptides spanning the entire gp 120 of HIV-1. At baseline, significant T-cell proliferation to pooled and individual peptides was observed in 15 ofthe 36 donors. After 12 months, proliferative responses to peptide pools were lost or decreased significantly in most donors. Responses appeared to fluctuate over time: at 12 months new recognition sites were detected in four of 10 donors showing T-cell proliferation at baseline, as well as in five of 15 donors with no previous proliferative responses. IL-2 production appeared to be a more sensitive and longer preserved parameter of T-helpter cell function: at baseline tbe majority of donors with no T-cell proliferation produced IL-2 in response to pooled peptides. Tbis response was not decreased significantly after 12 months. Tbe overall patterns of response to both pooled and individual peptides were heterogeneous among donors. Multiple recognition sites were detected in both variable and conserved regions of gpl20, but no pool or individual peptide was recognized by all responders. Functional T-cell responses were not statistically correlated to CD4+ cell percentile and absolute numbers.

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Section: Introductionmentioning

confidence: 99%

Kinetics and Specificities of the T Helper–Cell Response to GP120 in the Asymptomatic Stage of HIV–1 Infection

Geretti¹,

Baalen²,

Borleffs³

et al. 1994

Scand J Immunol

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“…Human immunodeficiency virus: Human immunodeficiency virus (HIV) is a retrovirus that continues to infect and kill millions of people every year, particularly in regions of socio‐economic disparity . Although chimpanzees suffer from an AIDS‐like SIVcpz immunopathology, HIV progression to AIDS occurs more frequently and is more severe in humans compared to chimpanzees . The causative mechanisms for this have never been unequivocally determined.…”

Section: Pathological Consequences Of Cmah Loss In Humansmentioning

confidence: 99%

“…The causative mechanisms for this have never been unequivocally determined. HIV, the HIV envelope proteins gp120 and gp41, and the HIV gag protein p24 elicit a strong proliferative response in chimpanzee lymphocytes, even after years of HIV infection . Conversely, human lymphocyte proliferative responses to HIV are relatively impaired compared to chimpanzee lymphocytes and this has been proposed as a mechanism of human AIDS susceptibility .…”

Section: Pathological Consequences Of Cmah Loss In Humansmentioning

confidence: 99%

“…HIV, the HIV envelope proteins gp120 and gp41, and the HIV gag protein p24 elicit a strong proliferative response in chimpanzee lymphocytes, even after years of HIV infection . Conversely, human lymphocyte proliferative responses to HIV are relatively impaired compared to chimpanzee lymphocytes and this has been proposed as a mechanism of human AIDS susceptibility . Others have proposed that human AIDS is attributed to a greater susceptibility of lymphocytes to apoptosis, potentially through differential expression of Siglecs .…”

Section: Pathological Consequences Of Cmah Loss In Humansmentioning

confidence: 99%

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Biochemical, Cellular, Physiological, and Pathological Consequences of Human Loss of N‐Glycolylneuraminic Acid

Okerblom

Varki

2017

ChemBioChem

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About 2–3 million years ago, Alu‐mediated deletion of a critical exon in the CMAH gene became fixed in the hominin lineage ancestral to humans, possibly through a stepwise process of selection by pathogen targeting of the CMAH product (the sialic acid Neu5Gc), followed by reproductive isolation through female anti‐Neu5Gc antibodies. Loss of CMAH has occurred independently in some other lineages, but is functionally intact in Old World primates, including our closest relatives, the chimpanzee. Although the biophysical and biochemical ramifications of losing tens of millions of Neu5Gc hydroxy groups at most cell surfaces remains poorly understood, we do know that there are multiscale effects functionally relevant to both sides of the host–pathogen interface. Hominin CMAH loss might also contribute to understanding human evolution, at the time when our ancestors were starting to use stone tools, increasing their consumption of meat, and possibly hunting. Comparisons with chimpanzees within ethical and practical limitations have revealed some consequences of human CMAH loss, but more has been learned by using a mouse model with a human‐like Cmah inactivation. For example, such mice can develop antibodies against Neu5Gc that could affect inflammatory processes like cancer progression in the face of Neu5Gc metabolic incorporation from red meats, display a hyper‐reactive immune system, a human‐like tendency for delayed wound healing, late‐onset hearing loss, insulin resistance, susceptibility to muscular dystrophy pathologies, and increased sensitivity to multiple human‐adapted pathogens involving sialic acids. Further studies in such mice could provide a model for other human‐specific processes and pathologies involving sialic acid biology that have yet to be explored.

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“…In most HIV-1-infected chimpanzees, no reduction in CD4 + T cell numbers, no decrease in response to recall antigens, and no overt and sustained increase in expression of activation markers or apoptosis is seen [40][41][42][43]. Furthermore, high proliferative responses against HIV as well as other pathogens, like cytomegalovirus, were noted [44,45].…”

Section: Introductionmentioning

confidence: 99%

Chimpanzee CD4⁺ T cells are relatively insensitive to HIV‐1 envelope‐mediated inhibition of CD154 up‐regulation

et al. 2008

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CD40-CD154 interaction forms a key event in regulation of crosstalk between dendritic cells and CD4 T cells. In human immunodeficiency virus (HIV)-1 infected patients CD154 expression is impaired, and the resulting loss of immune responsiveness by CD4+ T cells contributes to a progressive state of immunodeficiency in humans. Although chimpanzees are susceptible to chronic HIV-1/SIVcpz infection, they are relatively resistant to the onset of AIDS. This relative resistance is characterized by maintenance of CD4 + T cell populations and function, which is highly compromised in human patients. In our cohort of chronically HIV-1-and SIVcpz-infected chimpanzees, we demonstrated the capacity to produce IL-2, following CD3/CD28 stimulation, as well as preserved CD154 up-regulation. Cross-linking of CD4 with mAb was found to inhibit CD3/CD28-induced up-regulation of CD154 equally in chimpanzees and humans. However, specific cross-linking with trimeric recombinant HIV-1 gp140 revealed reduced sensitivity for inhibition of CD154 up-regulation in chimpanzees, requiring fourfold higher concentrations of viral protein. Chimpanzee CD4 + T cells are thus less sensitive to the immune-suppressive effect of low-dose HIV-1 envelope protein than human CD4 + T cells.Key words: Chimpanzee Á CD154 Á Cytokine Á HIV-1 Á Pathogenesis IntroductionHuman immunodeficiency virus type 1 (HIV-1) infection in humans is characterized by a precipitous loss of immune competence, eventually allowing the establishment of opportunistic infections and cancers [1,2]. This loss of immune function is ultimately observed at later stages as a peripheral decrease in the number of CD4 + T cells [3,4]. However, before the numerical loss of CD4 + T cells is apparent, HIV-1-infected individuals already have reduced antigen-specific and mitogen-stimulated CD4 + T cell responses [5][6][7][8][9][10][11][12]. These defects include diminished proliferative capacity and a functional loss in the ability to produce key cytokines. Induction of these important immunomodulatory cytokines is strongly dependent on dendritic cell (DC)-T cell interaction. Exposure to antigen will lead to DC activation [13][14][15], induce migration to lymphoid tissues and result in antigen presentation to T cells via MHC-TCR/CD3 interaction [16]. Subsequent activation of antigen-specific T cells leads to CD154 up-regulation which, via binding to CD40 on the DC, induces DC maturation, which is accompanied by up-regulation of the costimulatory molecules CD80 and CD86 and by IL-12 secretion [21,[27][28][29][30][31][32]. In addition, reduced capacity to produce IL-2 and consequential reduced antigen-specific T cell proliferation were reported [8,26], which can be restored via addition of IL-2 or via CD28 costimulation [5,33]. Cross-linking of CD4 with mAb or with HIV-1 envelope protein results in an inhibition of the CD3-mediated up-regulation of CD154 via an impairment of the normal CD3 signal transduction cascade [34,35]. This perturbation of the normal cell activation and CD154 upregulatory pat...

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T-cell responses to human immunodeficiency virus (HIV) and its recombinant antigens in HIV-infected chimpanzees

Cited by 60 publications

References 19 publications

Kinetics and Specificities of the T Helper–Cell Response to GP120 in the Asymptomatic Stage of HIV–1 Infection

Kinetics and Specificities of the T Helper–Cell Response to GP120 in the Asymptomatic Stage of HIV–1 Infection

Biochemical, Cellular, Physiological, and Pathological Consequences of Human Loss of N‐Glycolylneuraminic Acid

Chimpanzee CD4⁺ T cells are relatively insensitive to HIV‐1 envelope‐mediated inhibition of CD154 up‐regulation

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T-cell responses to human immunodeficiency virus (HIV) and its recombinant antigens in HIV-infected chimpanzees

Cited by 60 publications

References 19 publications

Kinetics and Specificities of the T Helper–Cell Response to GP120 in the Asymptomatic Stage of HIV–1 Infection

Kinetics and Specificities of the T Helper–Cell Response to GP120 in the Asymptomatic Stage of HIV–1 Infection

Biochemical, Cellular, Physiological, and Pathological Consequences of Human Loss of N‐Glycolylneuraminic Acid

Chimpanzee CD4+ T cells are relatively insensitive to HIV‐1 envelope‐mediated inhibition of CD154 up‐regulation

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Chimpanzee CD4⁺ T cells are relatively insensitive to HIV‐1 envelope‐mediated inhibition of CD154 up‐regulation