T Cell Function In Vitro Is An Independent Progression Marker For Aids In Human Immunodeficiency Virus-Infected Asymptomatic Subjects

Roos, M. T. L.; Miedema, Frank; Koot, M.; Tersmette, M.; Schaasberg, W.; Coutinho, Roel A.; Schellekens, P. T. A.

doi:10.1093/infdis/171.3.531

Cited by 78 publications

(38 citation statements)

References 19 publications

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“…In previous studies we demonstrated that in HIV-1 infection T cell reactivity to soluble CD3 MoAb measured in whole-blood lymphocyte cultures is an independent prognostic marker for progression to disease [12,23]. However, T cell responses to CD3 MoAb are relatively low with a tendency to have high coefficients of variation.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the expansion of CD8 CD28 ÿ cells was not specific for HIV-1 because this expansion was already seen in HIV -homosexual men at high risk. As we reported before, it is well feasible to test T cell reactivity to PHA and CD3 MoAb in whole-blood lymphocyte culture assays [12,23,32]. This is a simple, reproducible and suitable method for large routine screening/ monitoring of cohorts and patients enrolled in anti-retroviral drug trials.…”

Section: Discussionmentioning

confidence: 99%

“…Also the proportion of CD4 /CD28 drops but the decline is much less pronounced than the decrease of CD8 / CD28 proportion [19][20][21][22]. We have reported as well that in the Amsterdam cohort of HIV-1-infected men low T cell reactivity correlated with progression to AIDS [12,23].…”

Section: Introductionmentioning

confidence: 99%

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Low T cell reactivity to combined CD3 plus CD28 stimulation is predictive for progression to AIDS: correlation with decreased CD28 expression

Roos

Miedema

Meinesz

et al. 1996

Clinical and Experimental Immunology

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SUMMARYIn 219 HIV-1-infected men of the Amsterdam cohort we measured CD4 T cell numbers and in vitro T cell responses to CD3 MoAbs with or without CD28 costimulation and phytohaemagglutinin (PHA). The value of these markers was estimated for disease progression within 4 years. CD28 expression on T cells has been related to T cell responses. CD28 costimulation considerably enhanced T cell reactivity ( 8-10-fold) with lower coefficients of variation compared with reactivity to CD3 MoAb alone (median 5 versus 20). T cell reactivity to CD3 plus CD28 MoAb was decreased during HIV-1 infection and was besides CD4 T cell numbers the only independent predictor for progression to AIDS. Compared with the group with high CD4 T cell numbers the relative risk (RR) for the group with intermediate levels was 2 . 28, with low levels 5 . 20. In the groups with intermediate and low CD3 plus CD28 responses the RR was 2 . 04 and 4 . 16, respectively. The combined RR for both was 4 . 65 and 21 . 63. The independence of this marker was confirmed when the group with low CD4 T cell numbers was subdivided into groups with high, intermediate and low T cell responses. The expansion of CD8 CD28 ÿ T cells was already apparent in HIV ÿ homosexual men, but CD8 CD28 T cells specifically decreased in patients with AIDS. CD28 expression on T cells correlated moderately with T cell responses to CD3 plus CD28 MoAb. T cell reactivity to CD3 MoAb in the presence of CD28 MoAb is a stronger prognostic marker than T cell reactivity to CD3 MoAb alone.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Low T cell reactivity to combined CD3 plus CD28 stimulation is predictive for progression to AIDS: correlation with decreased CD28 expression

Roos

Miedema

Meinesz

et al. 1996

Clinical and Experimental Immunology

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“…T-cell proliferative capacity is an important independent predictor of progression to HIV disease [35,36] and can also serve to monitor immunological improvement after therapy [37,38]. Decreased proliferation of T-cells from HIV-infected individuals has been previously measured in response to in-vitro stimulation with CD3 monoclonal antibody, pokeweed mitogen, alloantigens, and recall antigens [39][40][41][42][43].…”

Section: Discussionmentioning

confidence: 99%

Effect of Antioxidant (Turmeric, Turmerin and Curcumin) on Human Immunodeficiency Virus

Cohly

Asad

Das

et al. 2003

IJMS

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pokeweed mitogen (PWM) were also examined in the presence of AZT and Tm. In the infection assay, T, Tm and Cu individually did not reduce p-24 antigen release or improve cell viability. AZT (5µM) + Tm (800 ng/ml) inhibited infection by 37 % and increased cell numbers by 30%; whereas, Tm (80 ng/ml) inhibited infection by 26% and increased cell number by 60%. In the proliferation assay, lymphocytes from HIV-infected patients showed better inhibition of mitogen responsiveness to Tm (800 ng/ml) when compared to AZT at 5 µM or Tm at 80 ng/ml. Turmerin inhibited HIV-infected T-cell proliferation and, in combination with AZT, decreased T-cell infection and increased cell viability. These data provide evidence suggesting that efficacious anti-HIV therapy may be possible using lower, less toxic doses of AZT in the presence of turmerin.

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“…At the onset of the AIDS epidemic, P. carinii pneumonia (PCP) 4 was a major cause of death in HIV-infected individuals. Today, the emergence of drug-resistant strains of HIV, the toxicity of antiretroviral agents, and economic factors limit both access to and the effectiveness of antiretroviral therapies, resulting in a large population of HIV-infected patients worldwide who are susceptible to PCP (2).…”

mentioning

confidence: 99%

T Cell Costimulatory Molecule Function Determines Susceptibility to Infection withPneumocystis cariniiin Mice

Beck

Blackmon

Rose

et al. 2003

The Journal of Immunology

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Loss of T cell number and function during HIV infection or secondary to pharmacologic immunosuppression renders individuals susceptible to opportunistic infections, including Pneumocystis carinii pneumonia. Because costimulatory receptors are critical for optimal T cell function, we hypothesized that these proteins would regulate susceptibility to opportunistic infections. We found that despite normal T cell numbers, mice deficient in the costimulatory molecules CD2 and CD28 spontaneously developed P. carinii pneumonia. In experiments using intratracheal injection of P. carinii organisms to induce infection, the loss of CD28 alone was sufficient to render mice susceptible to acute infection; however, the organism was eventually cleared. Examination of inflammatory responses to P. carinii revealed that mice deficient in both CD2 and CD28 accumulated CD8+ T cells in their lungs in response to infection and demonstrated markedly reduced specific Ab titers. Analysis of cytokine profiles suggested that regulation of IL-10 and IL-15 may be important elements of the response to this pathogen. Thus, costimulatory molecule function is critical in determining the initial susceptibility to infection with P. carinii. Analysis of immunologic responses in these mice may provide important insights into the defects that render individuals susceptible to opportunistic infection, and provide opportunities for novel immunologically based therapies.

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T Cell Function In Vitro Is An Independent Progression Marker For Aids In Human Immunodeficiency Virus-Infected Asymptomatic Subjects

Cited by 78 publications

References 19 publications

Low T cell reactivity to combined CD3 plus CD28 stimulation is predictive for progression to AIDS: correlation with decreased CD28 expression

Low T cell reactivity to combined CD3 plus CD28 stimulation is predictive for progression to AIDS: correlation with decreased CD28 expression

Effect of Antioxidant (Turmeric, Turmerin and Curcumin) on Human Immunodeficiency Virus

T Cell Costimulatory Molecule Function Determines Susceptibility to Infection withPneumocystis cariniiin Mice

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