Interleukin-2 production used to detect antigenic peptide recognition by T-helper lymphocytes from asymptomatic HIV-seropositive individuals

Clerici, Mario; Stocks, Naomi I.; Zajac, Robert A.; Boswell, R N; Bernstein, D.; Mann, Dean L.; Shearer, Gene M.; Berzofsky, Jay A.

doi:10.1038/339383a0

Cited by 205 publications

(89 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This greatly contrasted with the early defect in activation of T cells cocultured with Lps-treated Mo͞Mø (20), which could be compensated by increasing the number of ACs or addition of IL-2 (21). The lack of impairment of early events in T cell activation, including calcium flux and phosphotyrosine kinase activity, was observed in the T cells cocultured with HIVinfected ACs (22) or T cells isolated from HIV-infected individuals (1,23), suggesting a similar alteration with respect to accessory function of Tat-ACs and HIV-infected ACs. The partial activation of T cells is believed to be a critical factor for the maintenance of the infectious status, as HIV cannot infect resting T cells.…”

Section: Immunology: Wu and Schlossmanmentioning

confidence: 87%

Decreased ability of HIV-1 Tat protein-treated accessory cells to organize cellular clusters is associated with partial activation of T cells

Schlossman

1997

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

Section: Immunology: Wu and Schlossmanmentioning

confidence: 87%

Decreased ability of HIV-1 Tat protein-treated accessory cells to organize cellular clusters is associated with partial activation of T cells

Schlossman

1997

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Recombinant gp 120 was a generous gift from Genentech (San Francisco, CA). A group of five synthetic peptides corresponding to the env of HIV-1 (T1, T2, Th4.1, P18IIIB, and pl8MN) have been previously described (14,15). Mouse anti-human magnetic beads were purchased from Advanced Magnetic Inc. (Cambridge, MA).…”

Section: Methodsmentioning

confidence: 99%

Cytokine interactions in human immunodeficiency virus-infected individuals: roles of interleukin (IL)-2, IL-12, and IL-15.

Seder

Grabstein

Berzofsky

et al. 1995

The Journal of Experimental Medicine

108

View full text Add to dashboard Cite

SummaryCytokines have been shown to be powerful regulators of the immune response. In this study, we analyze the effect that the newly recognized cytokine interleukin (IL)-15 has on proliferation and cytokine induction using peripheral blood mononuclear cells (PBMCs) and purified CD4 § T cells from patients infected with human immunodeficiency virus (HIV) who are at various stages in their disease. We observed that IL-15 enhances the proliferative response in a dose-dependent manner from PBMCs of HIV-infected individuals when stimulated by polyclonal mitogen, tetanus toxoid, or HIV-specific antigen. The effects of exogenous IL-15 are substantially diminished by adding a neutralizing antibody to the [3 chain of the IL-2 receptor. Moreover, the ability of IL-15 to increase proliferation is enhanced by the presence of endogenous IL-2 produced in the cultures. The effect that exogenous IL-15 had on IL-2, IL-4, and interferon (IFN)-y induction from PBMC's or CD4 + T cells in response to mitogen or tetanus toxoid was also examined. This was compared to the effect that exogenous IL-2 and IL-12 had under the same conditions. Addition of IL-2 or IL-15 to short-term in vitro cultures of either PBMCs or CD4 + T cells had little effect on IL-2, IL-4, or IFN-~/production. By contrast, IL-12 caused substantial enhancement of both IL-2 and IFN-',/ production from these cultures. The role that endogenous cytokines have on IFN-y induction was also studied. Addition of a neutralizing antibody to the cx chain of the IL-2 receptor or IL-12 to antigen stimulated cultures caused a striking decrease in IFN-y production. Neutralization of endogenous IL-15 also resulted in diminished IFN-y production from cultures stimulated with mitogen. IL-4 and IFN-~/protein production by PBMCs and CD4 + T cells stimulated with mitogen was assessed to see if we could detect a specific bias of cytokine production. Small amounts oflL-4 were detected from CD4 + T cells but not PBMCs from most individuals tested. IFN-y and IL-2, however, were also produced from these same cultures. These results further elucidate the mechanism ofcytokine regulation in HIV-infected individuals, and they provide evidence that IL-15 may be a useful immune modulator.

show abstract

“…In that study, Converse et al [28] showed a specific deletion of T cells recognizing the major epitopes of CMV, a deletion that was specific for HIV-infected individuals, whereas T cell proliferation in response to minor epitopes remained comparable to controls. Similarly, the response to antigens encountered frequently (like env or influenza) is rapidly lost [29], whereas the response to rarely encountered antigens like allo-MHC antigens [29], or tetanus toxoid (H.G., personal observations) remains for a longer period. This model may also explain the relative heterogeneity of the results obtained in different studies analysing the T cell repertoire of HIV-infected patients [30][31][32][33][34][35].…”

Section: Discussionmentioning

confidence: 99%

Selective CD4+ T cell deletion after specific activation in HIV-infected individuals; protection by anti-CD28 monoclonal antibodies

Cottrez

Càpron

Groux

1996

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SUMMARYAIDS is characterized by a progressive decline in the number of CD4 T cells. This is preceded by an early selective defect in the proliferation of these cells to recall antigens [1][2][3], pokeweed mitogen (PWM) [4][5][6] and to superantigens (SAg) [4,7]. In contrast, the proliferative response to phytohaemagglutinin (PHA) remains intact [1,2,5]. We and others have shown that the proliferative defect in response to some stimuli was in fact due to the induction of cell death [4,7]. The activation-induced cell death mechanism that explains the proliferative defects observed in vitro might also account for the progressive in vivo deletion of CD4 T cells. Indeed, studies performed on different models of primates have shown that induction of cell death in CD4 T cells was detected only when T cells were isolated from animals infected with a type of retrovirus that induces an AIDS-like disease [8]. This correlation prompted us to analyse further the mechanism of HIV-induced activation cell death to determine the specificity and rate of induction of cell death. T cells from HIV-infected individuals were activated with superantigens and the V¯T cell receptor (TCR) expression analysed. Data presented here show that cell death is restricted to activated CD4 T cells, and does not affect bystander cells. More importantly, addition of anti-CD28 MoAb specifically inhibited the induction of apoptosis, raising possibilities for therapy.

show abstract

Interleukin-2 production used to detect antigenic peptide recognition by T-helper lymphocytes from asymptomatic HIV-seropositive individuals

Cited by 205 publications

References 11 publications

Decreased ability of HIV-1 Tat protein-treated accessory cells to organize cellular clusters is associated with partial activation of T cells

Decreased ability of HIV-1 Tat protein-treated accessory cells to organize cellular clusters is associated with partial activation of T cells

Cytokine interactions in human immunodeficiency virus-infected individuals: roles of interleukin (IL)-2, IL-12, and IL-15.

Selective CD4+ T cell deletion after specific activation in HIV-infected individuals; protection by anti-CD28 monoclonal antibodies

Contact Info

Product

Resources

About