Expansion of T cells negative for CD28 expression in hiv infection. Relation to activation markers and cell adhesion molecules, and correlation with prognostic markers

Kammerer, Robert; Iten, Anne; Frei, P. C.; Bürgisser, Philippe

doi:10.1007/s004300050010

Cited by 36 publications

(21 citation statements)

References 35 publications

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“…A marked decrease in telomere length has also been recorded in CD4, CD8 and B cells from HIV-infected patients with advanced immunodeficiency, supporting the notion of a high turnover of these cells and suggesting that replicative senescence may be involved in the final immunosuppression of these patients (323). There is also an increase in CD4 + CD28-negative cells in HIV infection, albeit not so marked as in the CD8 subset (324). Indeed, disease progression in AIDS is reported to be marked by an accumulation of CD28-negative cells unable to secrete IL 2, whereas long-term non-progressor patients maintain CD28 levels and IL 2 secretion capacity (325).…”

Section: Longevity Of Naive and Memory Cellsmentioning

confidence: 69%

T cells and aging update February 1999

Pawelec¹

1999

Front Biosci

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T cell immunosenescence 218effects of dysregulated immune responses in the elderly by supplementation or other approaches may result in an enhancement of their quality of life, and significant reductions in the cost of medical care in old age. FACTORS CONTRIBUTING TO IMMUNO-SENESCENCE HematopoiesisDysregulated hematopoiesis is seen in elderly individuals, raising the possibility that this could contribute to altered immune function in the aged. Hematopoiesis in man may be compromised because of a severely reduced capacity to produce colony stimulating factors (44) and increased production of pro-inflammatory factors such as IL 6 (45), because lower numbers of progenitor cells are present in the BM (46) and because of an age-related decline in proliferative potential of putative haematopoietic stem cells (HSC) (47). In mice, the repopulating potential of murine fetal liver-derived HSC is higher than that of adult BM-derived stem cells (48), suggesting possible aging of the HSC themselves. Normal cells with shorter telomeres possess less remaining replicative capacity than those with longer telomeres (see section 5.2). Accordingly, HSC from adult BM were found to have shorter telomeres than fetal liver-derived or umbilical cord-derived stem cells, consistent with aging of HSC (49). Telomere lengths decreased on culture despite low level expression of telomerase in these cells (50,51), although the rate of basepair loss per population doubling of cells in culture was lower during the first two weeks, when telomerase was upregulated, than in the next two, when it was downregulated (52). The telomerase expressed is therefore functionally active but may not be able to completely maintain telomere length in aging HSC cells. True embryonic stem cells (ESC), on the other hand, which may really be immortal, do retain high levels of telomerase activity (53). On the other hand, ESC from telomerase-knockout mice show gradual telomere shortening over many population doublings (PD) resulting in slowing and eventual cessation of growth (54). Certain animals which do not downregulate telomerase manifest a permanent growth phase and little or no senescence (55,56).

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Section: Longevity Of Naive and Memory Cellsmentioning

confidence: 69%

T cells and aging update February 1999

Pawelec¹

1999

Front Biosci

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“…Concomitant with a fall in CD28 ϩ IL-2 ϩ number, we noted the expansion of impaired Th cells, defined as the IL-2 ϩ subset that lacked CD28 (27)(28)(29). A striking difference was noted in the accumulation of the CD28 Ϫ IL-2 ϩ subset based on cell specificity.…”

Section: Ltnps Have Higher Frequencies Of P24-specific Cd28 ϩ Il-2 ϩ mentioning

confidence: 96%

“…In addition to IL-2, T cell proliferation is critically dependent on costimulation through the CD28 pathway (25,26), which is disrupted in HIV infection (27)(28)(29). We adopted the increasingly used strategy of stimulating blood cells with HIVspecific overlapping peptide panels and then enumerating the ensuing specific cytokine-producing cells by intracytoplasmic cell staining (ICS).…”

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confidence: 99%

Presence of HIV-1 Gag-Specific IFN-γ+IL-2+ and CD28+IL-2+ CD4 T Cell Responses Is Associated with Nonprogression in HIV-1 Infection

Boaz¹,

Waters

Murad

et al. 2002

The Journal of Immunology

221

155

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HIV immunity is likely CD4 T cell dependent. HIV-specific CD4 T cell proliferative responses are reported to correlate inversely with virus load and directly with specific CD8 responses. However, the phenotype and cytokine profile of specific CD4 T cells that correlate with disease is unknown. We compared the number/function of Gag p24-specific CD4 T cells in 17 HIV-infected long-term nonprogressors (LTNPs) infected for a median of 14.6 years with those of 16 slow progressors (SPs), also HIV infected for a median of 14 years but whose CD4 count had declined to <500 cells/μl. Compared with SPs, LTNPs had higher numbers of specific CD4s that were double positive for IFN-γ and IL-2 as well as CD28 and IL-2. However, CD4 T cells that produced IL-2 alone (IL-2+IFN-γ−) or IFN-γ alone (IFN-γ+IL-2−) did not differ between LTNPs and SPs. The decrease in p24-specific CD28+IL-2+ cells with a concomitant increase of p24-specific CD28−IL-2+ cells occurred before those specific for a non-HIV Ag, CMV. p24-specific CD28−IL-2+ cells were evident in LTNPs and SPs, whereas the CMV-specific CD28−IL-2+ response was confined to SPs. The difference between LTNPs and SPs in the Gag p24 IFN-γ+IL-2+ response was maintained when responses to total Gag (p17 plus p24) were measured. The percentage and absolute number of Gag-specific IFN-γ+IL-2+ but not of IFN-γ+IL-2− CD4s correlated inversely with virus load. The Gag-specific IFN-γ+IL-2+ CD4 response also correlated positively with the percentage of Gag-specific IFN-γ+ CD8 T cells in these subjects. Accumulation of specific CD28−IL-2+ helpers and loss of IFN-γ+IL-2+ CD4 T cells may compromise specific CD8 responses and, in turn, immunity to HIV.

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“…In HIV infection, there is an increased proportion of activated/memory T cells that do not express CD28 (19,28,48,62).…”

mentioning

confidence: 99%

Human Immunodeficiency Virus-Specific Circulating CD8 T Lymphocytes Have Down-Modulated CD3ζ and CD28, Key Signaling Molecules for T-Cell Activation

Trimble

Shankar

Patterson

et al. 2000

J Virol

113

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Expansion of T cells negative for CD28 expression in hiv infection. Relation to activation markers and cell adhesion molecules, and correlation with prognostic markers

Cited by 36 publications

References 35 publications

T cells and aging update February 1999

T cells and aging update February 1999

Presence of HIV-1 Gag-Specific IFN-γ+IL-2+ and CD28+IL-2+ CD4 T Cell Responses Is Associated with Nonprogression in HIV-1 Infection

Human Immunodeficiency Virus-Specific Circulating CD8 T Lymphocytes Have Down-Modulated CD3ζ and CD28, Key Signaling Molecules for T-Cell Activation

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