Expansion of CMV-specific CD8+CD45RA+CD27- T cells in B-cell chronic lymphocytic leukemia

Mackus, Wendelina J. M.; Frakking, Florine N. J.; Grummels, Annette; Gamadia, Laila E.; Bree, Godelieve J. de; Hamann, Dörte; Lier, R. A. W. Van; Oers, Marinus H. J. van

doi:10.1182/blood-2003-01-0182

Cited by 93 publications

(92 citation statements)

References 49 publications

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“…The above findings suggested a connection between the number of virus-specific T cells in latency and their phenotype which would accord with the expansion of CMV-specific CD8 ϩ CD27 Ϫ T cells in immunocompromised patients (11,22), B cell chronic lymphocytic leukemia patients (23), and the elderly (24,25).…”

Section: The Cd27 ϫ Phenotype Is Correlated With the Magnitude Of Thementioning

confidence: 72%

The Size and Phenotype of Virus-Specific T Cell Populations Is Determined by Repetitive Antigenic Stimulation and Environmental Cytokines

Gamadia

Leeuwen

Remmerswaal³

et al. 2004

The Journal of Immunology

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108

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Based on the expression of the TNFR SFP CD27, two Ag-primed CD8+ T cell subsets can be discerned in the circulation of healthy individuals: CD27+ T cells that produce a variety of cytokines but do not display immediate cytolytic activity; and cytotoxic CD27− T cells, which secrete only IFN-γ and TNF-α. The mechanism that controls the generation of these different phenotypes is unknown. We show that CMV reactivation not only increases the number of virus-specific T cells but also induces their transition from a CD27+ to a CD27− phenotype. In support of a relation between pool size and phenotype in a cohort of latently infected individuals, the number of Ag-specific CD27− CD8+ T cells was found to be linearly related to the total number of CMV-specific CD8+ T cells. In vitro studies revealed that the acquisition of the CD27− phenotype on CMV-specific T cells depended on the interaction of CD27 with its cellular ligand, CD70. Expression of CD70 was proportional to the amount of antigenic stimulation and blocked by the CD4+ T cell-derived cytokine IL-21. Thus, induction of CD70, which may vary in distinct viral infections, appears to be a key factor in determining the size and phenotype of the CMV-specific T cell population in latently infected individuals.

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Section: The Cd27 ϫ Phenotype Is Correlated With the Magnitude Of Thementioning

confidence: 72%

The Size and Phenotype of Virus-Specific T Cell Populations Is Determined by Repetitive Antigenic Stimulation and Environmental Cytokines

Gamadia

Leeuwen

Remmerswaal³

et al. 2004

The Journal of Immunology

Self Cite

108

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“…However, there is now interest in the potential health associations of chronic viral carriage in a range of clinical settings, particularly in patients with B‐CLL in whom the CMV‐specific T cell immune response can expand to a remarkably high frequency 15, 16. Despite this, no published epidemiological data exists investigating the relationship between CMV and B‐CLL prognosis.…”

Section: Discussionmentioning

confidence: 99%

“…The CD4:CD8 ratio is markedly lower in CMV seropositive individuals compared with those who remain uninfected, and this effect is particularly profound in patients with CLL. Indeed, one of the paradoxes of CMV infection in patients with CLL is that the magnitude of the virus‐specific immune response is actually higher than in healthy individuals, despite the state of immune suppression, in a mechanism that is believed to be a response to increased levels of subclinical viral reactivation 15, 16. As such there is now considerable interest in how chronic CMV infection may influence the clinical profile of patients with B‐CLL 17.…”

Section: Introductionmentioning

confidence: 99%

Cytomegalovirus infection does not impact on survival or time to first treatment in patients with chronic lymphocytic leukemia

et al. 2016

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Human cytomegalovirus (HCMV) is a widely prevalent herpes virus which establishes a state of chronic infection. The establishment of CMV‐specific immunity controls viral reactivation and leads to the accumulation of very large numbers of virus‐specific T cells which come to dominate the immune repertoire. There is concern that this may reduce the immune response to heterologous infections and HCMV infection has been associated with reduced survival in elderly people. Patients with chronic lymphocytic leukemia (B‐CLL) suffer from a state of immune suppression but have a paradoxical increase in the magnitude of the CMV‐specific T cell and humoral immune response. As such, there is now considerable interest in how CMV infection impacts on the clinical outcome of patients with B‐CLL. Utilizing a large prospective cohort of patients with B‐CLL (n = 347) we evaluated the relationship between HCMV seropositivity and patient outcome. HCMV seropositive patients had significantly worse overall survival than HCMV negative patients in univariate analysis (HR = 2.28, 95% CI: 1.34–3.88; P = 0.002). However, CMV seropositive patients were 4 years older than seronegative donors and this survival difference was lost in multivariate modeling adjusted for age and other validated prognostic markers (P = 0.34). No significant difference was found in multivariate modeling between HCMV positive and negative patients in relation to the time to first treatment (HR = 1.12, 95% CI: 0.68–1.84; P = 0.65). These findings in a second independent cohort of 236 B‐CLL patients were validated. In conclusion no evidence that HCMV impacts on the clinical outcome of patients with B‐CLL was found. Am. J. Hematol. 91:776–781, 2016. © 2016 Wiley Periodicals, Inc.

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“…36 These data are in line with observations in B-cell chronic lymphocytic leukemia patients, where an expansion of CD8 þ T cells was related to CMV infection. 37 There also seems to be a potent stimulation of T cell function by subclinical CMV infections. 18 Furthermore, T cell recovery was suggested to be influenced by the anti-viral treatment itself, 38 when ganciclovir prophylaxis and pre-emptive therapy were compared, but these treatment-related observations were not made consistently.…”

Section: Discussionmentioning

confidence: 99%

Lymphocyte reconstitution following allogeneic hematopoietic stem cell transplantation: a retrospective study including 148 patients

Heining

Spyridonidis

Bernhardt

et al. 2007

Bone Marrow Transplant

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Here we investigated the influence of parameters known before hematopoietic stem cell transplantation (HSCT) as well as the relevance of graft-versus-host disease (GvHD) and cytomegalovirus (CMV) reactivation on post transplant lymphocyte reconstitution in 148 patients treated in our institution between 1996 and 2003. Median patient age was 42 (19-68) years, HSCT followed standard high dose (n ¼ 91) or reduced-intensity conditioning regimens (n ¼ 57) with bone marrow (BM, n ¼ 67) or peripheral blood stem cells (PBSC, n ¼ 81) from related (n ¼ 71) or unrelated (n ¼ 77) donors. In the first months, we observed a partially faster reconstitution of CD3 þ 4 þ , CD3 þ 8 þ and CD4 þ 45RA þ T cells in patients following peripheral blood stem cell transplantation when compared to bone marrow transplantation. Prolonged CD3 þ 4 þ and CD4 þ 45RA þ lymphopenia was noted after unrelated donor HSCT and GvHD prophylaxis containing anti-T-lymphocyte globulin. Lymphocyte subset counts in patients older than the median age were comparable to those in patients transplanted at a younger age and not influenced by the conditioning regimen. CD3 þ 8 þ T cell reconstitution was strongly correlated with CMV reactivation, but not significantly affected by CMV serostatus before HSCT. Incidence or extent of GvHD did not significantly influence lymphocyte reconstitution. Therefore, the source of graft is the most predictive parameter in early lymphocyte reconstitution, but the differences in lymphocyte recovery completely resolved within the first year after HSCT.

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Expansion of CMV-specific CD8+CD45RA+CD27- T cells in B-cell chronic lymphocytic leukemia

Cited by 93 publications

References 49 publications

The Size and Phenotype of Virus-Specific T Cell Populations Is Determined by Repetitive Antigenic Stimulation and Environmental Cytokines

The Size and Phenotype of Virus-Specific T Cell Populations Is Determined by Repetitive Antigenic Stimulation and Environmental Cytokines

Cytomegalovirus infection does not impact on survival or time to first treatment in patients with chronic lymphocytic leukemia

Lymphocyte reconstitution following allogeneic hematopoietic stem cell transplantation: a retrospective study including 148 patients

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