Cytomegalovirus-specific T-cell responses and viral replication in kidney transplant recipients

Egli, Adrian; Binet, Isabelle; Binggeli, S.; Jäger, Clemens; Dumoulin, Alexis; Schaub, Stefan; Steiger, Juerg; Sester, Urban; Sester, Martina; Hirsch, Hans H.

doi:10.1186/1479-5876-6-29

Cited by 105 publications

(91 citation statements)

References 39 publications

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“…Relating to this, it has been shown recently that only responses directed against pp65 correlate with protection from viremia, whereas another study adversatively highlighted the importance of IE-1 (21,23). Also, a lack of CD4+ T cell help, which might have been caused by the high dosed immunosuppression, could provide a plausible explanation for the simultaneous detection of high-level HCMV DNAemia and specific CD8+ T cell responses, as it has been demonstrated recently that CD8+ T cells alone are not sufficient to control HCMV infection and that kidney transplant recipients with specific CD4+ T cell responses are protected from HCMV replication when the immunosuppression is stable (20,24,35). Because LuTRs may be infected by multiple HCMV strains, incomplete cross-protection by CD8+ T cells against a de novo donor-transmitted virus strain could also have been played a role, which would be strengthened by the fact that three of the four patients mentioned above displayed a D+/R+ constellation and were therefore infected with at least two different HCMV strains (36,37).…”

Section: Discussionmentioning

confidence: 99%

Prospective Analysis of Human Cytomegalovirus DNAemia and Specific CD8+ T Cell Responses in Lung Transplant Recipients

Weseslindtner

Kerschner

Steinacher

et al. 2012

American Journal of Transplantation

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In lung transplant recipients (LuTRs), human cytomegalovirus (HCMV) DNAemia may be associated with HCMV disease and reduced survival of the allograft. Because T cells are essential for controlling HCMV replication, we investigated in this prospective study whether the kinetics of plasma HCMV DNA loads in LuTRs are associated with HCMV-specific CD8+ T cell responses, which were longitudinally assessed using a standardized assay. Sixty-seven LuTRs were monitored during the first year posttransplantation, with a mean of 17 HCMV DNA PCR quantifications and 11.5 CD8+ T cell tests performed per patient. HCMV-specific CD8+ T cell responses displayed variable kinetics in different patients, differed significantly before the onset of HCMV DNAemia in LuTRs who subsequently experienced episodes of DNAemia with high (>1000 copies/mL) and low plasma DNA levels (p = 0.0046, Fisher's exact test), and were absent before HCMV disease. In HCMV-seropositive LuTRs, highlevel DNAemia requiring preemptive therapy occurred more frequently when HCMV-specific CD8+ T cell responses fluctuated, were detected only after HCMV DNA detection, or remained undetectable (p = 0.0392, Fisher's exact test). Thus, our data indicate that HCMVspecific CD8+ T cells influence the magnitude of HCMV DNAemia episodes, and we propose that a standardized measurement of CD8+ T cell immunity might contribute to monitoring the immune status of LuTRs posttransplantation.

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Section: Discussionmentioning

confidence: 99%

Prospective Analysis of Human Cytomegalovirus DNAemia and Specific CD8+ T Cell Responses in Lung Transplant Recipients

Weseslindtner

Kerschner

Steinacher

et al. 2012

American Journal of Transplantation

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“…CMV-specific cellular immune responses were measured in 51 samples from 24 CMV IgG-seropositive cases and in 98 samples from 59 IgG-seropositive controls. For CMV-specific PBMC stimulation, corresponding 15-mer peptide pools spanning CMV pp65 were used (14). Gamma interferon spots were counted by using an ESA reader (Cellular Technologies Ltd., Shaker Heights, OH).…”

Section: Methodsmentioning

confidence: 99%

JC Virus-Specific Immune Responses in Human Immunodeficiency Virus Type 1 Patients with Progressive Multifocal Leukoencephalopathy

Khanna

Wolbers

Mueller

et al. 2009

J Virol

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Progressive multifocal leukoencephalopathy (PML) is a frequently fatal disease caused by uncontrolled polyomavirus JC (JCV) in severely immunodeficient patients. We investigated the JCV-specific cellular and humoral immunity in the Swiss HIV Cohort Study. We identified PML cases (n ‫؍‬ 29), as well as three matched controls per case (n ‫؍‬ 87), with prospectively cryopreserved peripheral blood mononuclear cells and plasma at diagnosis. Nested controls were matched according to age, gender, CD4؉ T-cell count, and decline. Survivors (n ‫؍‬ 18) were defined as being alive for >1 year after diagnosis. Using gamma interferon enzyme-linked immunospot assays, we found that JCV-specific T-cell responses were lower in nonsurvivors than in their matched controls (P ‫؍‬ 0.08), which was highly significant for laboratory-and histologically confirmed PML cases (P ‫؍‬ 0.004). No difference was found between PML survivors and controls or for cytomegalovirus-specific T-cell responses. PML survivors showed significant increases in JCV-specific T cells (P ‫؍‬ 0.04) and immunoglobulin G (IgG) responses (P ‫؍‬ 0.005). IgG responses in survivors were positively correlated with CD4 ؉ T-cell counts (P ‫؍‬ 0.049) and negatively with human immunodeficiency virus RNA loads (P ‫؍‬ 0.03). We conclude that PML nonsurvivors had selectively impaired JCV-specific T-cell responses compared to CD4 ؉

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“…CMV infection does not cause any disease and show any clinical symptoms in an immunocomplement body, but does in immunodeficiency or immunocompromised body, such as patients with acquired immune deficiency syndrome (AIDS) or organ transplant recipients. It can lead to inflammatory reactions mainly in genitourinary system, central nervous system and liver, and even develop severe deficiency in the immune system or death (1).…”

Section: Introductionmentioning

confidence: 99%

Analysis of the Conservation of T Cell Receptor Alpha and Beta Chain Variable Regions Gene in pp65 Peptide-Specific HLA-A*0201-Restricted CD8+ T Cells

Luo

Wen

et al. 2009

Cell Mol Immunol

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Cytomegalovirus-specific T-cell responses and viral replication in kidney transplant recipients

Cited by 105 publications

References 39 publications

Prospective Analysis of Human Cytomegalovirus DNAemia and Specific CD8+ T Cell Responses in Lung Transplant Recipients

Prospective Analysis of Human Cytomegalovirus DNAemia and Specific CD8+ T Cell Responses in Lung Transplant Recipients

JC Virus-Specific Immune Responses in Human Immunodeficiency Virus Type 1 Patients with Progressive Multifocal Leukoencephalopathy

Analysis of the Conservation of T Cell Receptor Alpha and Beta Chain Variable Regions Gene in pp65 Peptide-Specific HLA-A*0201-Restricted CD8+ T Cells

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