Lymphocyte activation in HIV-1 infection. II. Functional defects of CD28− T cells

Borthwick, Nicola; Bofill, Margarita; Gombert, Wendy M.; Akbar, Arne N.; Medina, Eva; Sagawa, Kimitaka; Lipman, Marc; Johnson, Margaret; Jánossy, G.

doi:10.1097/00002030-199404000-00004

Cited by 193 publications

(133 citation statements)

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“…The proportion of CD57 + CD28 -cells was quite large in some of our patients, and of the same order of magnitude as reported for non-symptomatic HIV-infected individuals (CDC stages I-IV) [1].…”

Section: Discussionsupporting

confidence: 86%

“…If CD28 -T cell expansion really was to signal the onset of immunodeficiency, this would have to be expected in many clinical conditions. As a matter of fact, there are no clinical data to sustain that CD28 -CD8 + T cell expansion in itself leads to the development of opportunistic infections, since, according to Borthwick and coworkers' own data [1], CD28 -T cells expand in asymptomatic HIV-infected individuals from CDC stages I-III, but in CDC stage IV the CD28 -CD57 + subset decreases. It was in fact suggested by Lewis and coworkers that, conversely, it may be the very disappearance of HIV-specific CTL (CD8 + CD28 -?)…”

Section: Discussionmentioning

confidence: 99%

“…The fact that, unlike in CD57 -cells, there was no message for the IL-2R -chain in CD57 + cells may explain why Lewis and colleagues [4] were unsuccessful when attempting to reduce the amount of DNA fragmentation in cultured CD28 -CD57 + CD8 + T cells by the addition of IL-2, which normally prevents apoptosis in T cells. Several authors who observed an in vitro proliferative defect of CD8 + CD28 -T cells in HIV infection [1,4] tied this to the absence of the CD28 surface antigen, which, they explained, could be instrumental in the development of immunodeficiency. If CD28 -T cell expansion really was to signal the onset of immunodeficiency, this would have to be expected in many clinical conditions.…”

Section: Discussionmentioning

confidence: 99%

“…This may occur in the absence of clinical symptoms [1][2][3][4]. Notably, in their publication on lymphocyte activation in HIV infection, Borthwick and coworkers [1] reported in 1994 that CD57 + T cells were almost exclusively CD28 -in HIVinfected individuals. They confirmed this finding in healthy controls, where, however, the overall proportion of CD57 + T cells was much smaller.…”

Section: Introductionmentioning

confidence: 99%

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The enigma of CD57+CD28– T cell expansion—anergy or activation?

Kern

Ode-Hakim

Vogt

et al. 1996

Clinical and Experimental Immunology

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Expansion of a CD57+CD8+ T lymphocyte subset has been reported in HIV and human cytomegalovirus (HCMV) infection. Almost all of these T cells lack CD28 expression. While CD28– cells are often associated with anergy, some authors believe their expansion in HIV infection precipitates immunodeficiency. We studied 15 randomly chosen patients with immune activation and observed that CD57+CD28– T cell expansion may occur in various conditions and to the same degree as in HIV infection without resulting in immunodeficiency. Triple colour flow cytometry also revealed that the CD57 and CD28 antigens are coexpressed in only 3% of CD8+ T cells, irrespective of the underlying condition, so that almost all CD57+CD8+ cells are always CD28–. Analysis of Fas (CD95) expression with respect to CD28 expression on CD4+ and CD8+ T cells from 10 additional patients indicated no increased commitment to apoptosis in CD28– T cells. Semiquantitative polymerase chain reaction (PCR) comparing CD28+ and CD28–CD8+ T cells with respect to cytokine gene expression (tumour necrosis factor‐alpha (TNF‐α), interferon‐gamma (IFN‐γ), IL‐1β) in five renal transplant patients with expansion of the CD57+ subset detected no cytokine gene expression deficit in CD28– T cells. A direct association of increased proportions of CD57+CD28–CD8+ T cells with immunodeficiency/anergy is disputed.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The enigma of CD57+CD28– T cell expansion—anergy or activation?

Kern

Ode-Hakim

Vogt

et al. 1996

Clinical and Experimental Immunology

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show abstract

“…Increased CD57 or CD11b T cell subset in PBMC has been reported after BMT [21] or in the course of infection by cytomegalovirus [22] and Epstein-Barr virus (EBV) [23]. Recently, an increased proportion of CD28 ÿ T cells was also reported in HIV infection [39][40][41]. In such clinical situations, lymphoproliferative and/or subsequent lymphoatrophic states are often observed in their clinical courses.…”

Section: Discussionmentioning

confidence: 99%

Preferential elimination of CD28+ T cells in systemic lupus erythematosus (SLE) and the relation with activation-induced apoptosis

Kaneko

Saito

Hashimoto

et al. 1996

Clinical and Experimental Immunology

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SUMMARYCD28 on T cells provides a potent costimulatory signal for T cell activation. Down-regulation of CD28 on peripheral T cells has been reported in certain clinical conditions, but full studies on the mechanism and biological significance have not been performed. Our extensive phenotype analysis of peripheral blood lymphocytes (PBL) from SLE patients revealed that the absolute number of CD28 T cells of both CD4 and CD8 phenotypes was selectively decreased, while that of CD28 ÿ T cells was maintained. CD28 T cells from SLE patients exhibited mostly normal proliferative responses to both CD28-dependent and -independent stimulations. In contrast, CD28 ÿ T cells were hyporesponsive to anti-CD3 stimulation in both SLE and normal controls. These results implied that the selective decrease of CD28 T cells in SLE does not result from a hyporesponsiveness of CD28 T cells. To investigate the reason for the selective loss of CD28 T cells, we determined the appearance of apoptotic cells in culture with or without anti-CD3 stimulation. Apoptotic cells defined by merocyanine (MC)540 were gradually increased from 12 h to 24 h. Anti-CD3-induced apoptosis of CD28 T cells was significantly accelerated in SLE, whereas apoptosis of CD28 ÿ T cells was hardly detected in both SLE and normal controls. Comparative analysis between CD28 and CD28 ÿ T cells on CD95 (Fas) and Bcl-2 expression, which are related to activation-induced cell death (AICD), did not show a major difference, although CTLA4, which has been demonstrated to transmit an apoptosis-inducing signal, was expressed only on CD28 T cells. Our results suggest that CD28-mediated costimulation influences T cell susceptibility to AICD and may be involved in T cell lymphopenia in SLE.

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Dysregulation of the interleukin-2 receptor ?- and ?-chain expression in CD4 and CD8 T cells in HIV infection

Johnson

Parkin

1997

Cytometry

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Peripheral blood mononuclear cells were prepared from human immunodeficiency virus‐positive (HIV+) individuals (n = 46) to investigate the expression of both chains of the interleukin‐2 receptor. Both qualitative and quantitative changes in expression were observed. Total lymphocyte expression of the IL‐2α chain (CD25) was decreased compared with HIV‐negative (HIV−) controls. This was due to the decrease in the CD4+ population, which favored expression of this receptor, rather than a decrease in expression, per se. CD8+ lymphocytes expressed the β chain (CD122) in the absence of the α chain. However, a significant increase in the number of peripheral blood CD8+ lymphocytes expressing mainly the β subunit was observed in HIV+ patients (P = 0.02). This was observed to a similar extent in asymptomatic and symptomatic patients and characterized a subpopulation of T lymphocytes expressing high levels of CD8. Lymphocytes from patients with advanced HIV disease failed to up‐regulate both α and β chains in response to mitogenic concentrations of phytohaemagglutanin. However, those cells that were able to up‐regulate both of the IL‐2 receptors were capable of effective signal transduction through the receptor, increasing the proliferative response to stimulation. Cytometry 30:289–295, 1997. © 1998 Wiley‐Liss, Inc.

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Lymphocyte activation in HIV-1 infection. II. Functional defects of CD28− T cells

Cited by 193 publications

References 0 publications

The enigma of CD57+CD28– T cell expansion—anergy or activation?

The enigma of CD57+CD28– T cell expansion—anergy or activation?

Preferential elimination of CD28+ T cells in systemic lupus erythematosus (SLE) and the relation with activation-induced apoptosis

Dysregulation of the interleukin-2 receptor ?- and ?-chain expression in CD4 and CD8 T cells in HIV infection

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