Lack of Epstein-Barr virus- and HIV-specific CD27− CD8+ T cells is associated with progression to viral disease in HIV-infection

Baarle, Debbie van; Kostense, Stefan; Hovenkamp, E.; Ogg, Graham S.; Nanlohy, Nening M.; Callan, Margaret; Dukers, Nicole H. T. M.; McMichael, Andrew J.; Oers, Marinus H. J. van; Miedema, Frank

doi:10.1097/00002030-200210180-00004

Cited by 67 publications

(77 citation statements)

References 37 publications

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“…In contrast, after infection with LCMV the majority of gp33-specific CTL retained CD27 expression. The retained CD27 expression on memory CTL following infection with LCMV was unexpected since T cell proliferation and differentiation to effector cells has been correlated with loss of CD27 expression [10,14,23]. To further substantiate our observation, memory CTL specific for different LCMV antigens were analyzed 100 days after infection in secondary lymphoid organs and in the circulation.…”

Section: Cd27 Expression On Memory Ctlsupporting

confidence: 59%

“…Therefore, the differentiation of the memory CTL population may reflect unique properties of the particular viral infection. Persistent CD27 expression has been associated with impaired effector function of EBV-and HIV-specific CTL [10,13,14]. However, in vitro work and recent studies in recombinant mice have provided evidence that the CD27-CD70 interaction provides a costimulatory signal to T cells [15][16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

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Virus-induced polyclonal B cell activation improves protective CTL memoryvia retained CD27 expression on memory CTL

et al. 2005

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Different viruses elicit distinct phenotypes of memory cytotoxic T lymphocytes (CTL). This is reflected in differential expression of homing receptors and costimulatory molecules like CD27. Memory CTL retained CD27 following lymphocytic choriomeningitis virus (LCMV) infection, but not after immunization with recombinant vaccinia virus or tumor cells expressing LCMV glycoprotein. Stable CD27 expression on memory CTL required ligation by CD70 expressed on polyclonally activated B cells during the contraction phase. The functional consequence of CD27 expressed on virus-specific CTL was analyzed in CD27-deficient mice. LCMV infection of CD27 -/-mice revealed that primary CTL activation and expansion as well as elimination of the virus were independent of CD27 expression. In contrast, ligation of CD27 on memory CTL upon secondary antigen encounter increased clonal expansion and improved protection against re-infection. This points to novel B cell-CTL interactions during viral infection and to a beneficial role of polyclonal B cell activation that represents a characteristic of murine LCMV, human immunodeficiency virus and human hepatitis B and C virus infection.

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Section: Cd27 Expression On Memory Ctlsupporting

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Virus-induced polyclonal B cell activation improves protective CTL memoryvia retained CD27 expression on memory CTL

et al. 2005

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“…10,22 In these studies, virus-specific CD8 ϩ T cells accumulate in the CD45R0 ϩ CD27 ϩ CCR7 Ϫ subset and display none of the features normally associated with cytotoxic effector function. The finding that a direct correlation exists between number and phenotype of virus-specific CD8 ϩ T cells and the level of plasma viral load 23,24 corroborates that functional maturation of CD8 ϩ T cells is of prime importance in maintaining viral latency.…”

Section: Introductionmentioning

confidence: 62%

Primary immune responses to human CMV: a critical role for IFN-γ–producing CD4+ T cells in protection against CMV disease

Gamadia

Remmerswaal

Weel

et al. 2003

Blood

383

335

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The correlates of protective immunity to disease-inducing viruses in humans remain to be elucidated. We determined the kinetics and characteristics of cytomegalovirus (CMV)-specific CD4 ؉ and CD8 ؉ T cells in the course of primary CMV infection in asymptomatic and symptomatic recipients of renal transplants. Specific CD8 ؉ cytotoxic T lymphocyte (CTL) and antibody responses developed regardless of clinical signs. CD45RA ؊ CD27 ؉ CCR7 ؊ CTLs, although classified as immature effector cells in HIV infection, were the predominant CD8 effector population in the acute phase of protective immune reactions to CMV and were functionally competent. Whereas in asymptomatic individuals the CMV-specific CD4 ؉ T-cell response preceded CMV-specific CD8 ؉ T-cell responses, in symptomatic individuals the CMV-specific effectormemory CD4 ؉ T-cell response was delayed and only detectable after antiviral therapy.The appearance of disease symptoms in these patients suggests that functional CD8 ؉ T-cell and antibody responses are insufficient to control viral replication and that formation of effector-memory CD4 ؉ T cells is necessary for recovery of infection.

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“…Finally, the last hypothesis, which is the one that we favor, is that CMV-specific T lymphocytes are not fully functional in fetuses. In line with this interpretation, an increased number of studies concluded to impaired function of CD8 ϩ T cells based on data showing a dissociation between the number of CD8 ϩ T cells primed with viruses and the number of T cells that respond to the corresponding viral antigens by IFN-␥ production (23)(24)(25)(26). Comparing IFN-␥ responses with CMV during primary infection in both fetuses and adults should definitely demonstrate whether CD8 response to CMV is less intense in early age.…”

Section: Discussionmentioning

confidence: 97%

Cellular Immune Response of Fetuses to Cytomegalovirus

et al. 2004

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Primary infection with cytomegalovirus (CMV) in immunocompetent hosts is accompanied with activation and differentiation of naive CD8ϩ T cells to effector/memory cells secreting interferon-␥ (IFN-␥). Alteration of these responses during the perinatal period is suggested by a higher rate of CMV diseases in congenital infection. For addressing this issue, immunologic investigations were performed in 15 fetuses (22-36 wk of gestation) with documented congenital CMV infection. Results show that cellular immune responses can be detected as soon as the 22nd week of gestation (the youngest fetus analyzed). Compared with age-matched control subjects, infected fetuses evidence a dramatic increase in the percentages of activated and terminally differentiated CD8 T cells. Indeed, median percentages (interquartile range) of HLA-DR ϩ and of CD28 Ϫ CD8 ϩ T cells were 24% (19 -34) and 38% (24 -52), respectively in infected fetuses versus 3% (0 -4) for each subset in control subjects. In addition, the percentages of T cells secreting IFN-␥ after in vitro stimulation with phorbol myristate acetate and CD8ϩ T lymphocytes are believed to be an important host defense against viruses. This concept is supported by the fact that patients with defects in cellular immunity experience more prolonged virus shedding and present more frequent and severe illness with cytomegalovirus (CMV) (1, 2). Furthermore, viral immunity to CMV can be restored by the adoptive transfer of CMV-specific CD8 ϩ T cells in immunodeficient individuals (3).During primary infection with CMV, CD8 ϩ T cells are activated, proliferate, and differentiate to become effector and memory lymphocytes. Effector/memory CD8 ϩ T cells possess cytotoxic activity. In addition, they become capable of releasing factors with antiviral action, such as interferon-␥ (IFN-␥) (4). Activation and differentiation of CD8 ϩ T cells during viral infection are associated with changes in the cell surface phenotype. In persistent virus infections, HLA-DR expression on CD8 ϩ T cells reflects immune activation (5). Also, during the course of infection, part of CD8 T cells switch progressively to a long-lived CD8 ϩ CD28 Ϫ T-cell pool (6), which contains virus-specific, cytolytic T lymphocytes (7,8). It has been suggested that these CD28 Ϫ CD8 ϩ T cells might be terminally differentiated because of their poor proliferative potential (9).The great majority of primary CMV infections in immunocompetent hosts are clinically silent, whereas the rate of CMV disease is 10 -15% in congenital infection (10). This difference is supposed to be related to the immaturity of the immune system. The concept of immaturity of CD8 ϩ T-cell functional responses to viruses has been largely documented in mouse models (11,12) and also suggested in the human. As an example, the incidence of children who are younger than 6 mo of age and develop CD8 T-cell activities, as measured by cytotoxicity (13, 14) or IFN-␥ secretion (15)

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Lack of Epstein-Barr virus- and HIV-specific CD27− CD8+ T cells is associated with progression to viral disease in HIV-infection

Abstract: Taken together, our data indicate that virus-specific CD27- T cells may be important effector T cells in controlling chronic viral infections in humans and that lack of differentiation into CD27- effector T cells may lead to progression of viral disease.

Cited by 67 publications

References 37 publications

Virus-induced polyclonal B cell activation improves protective CTL memoryvia retained CD27 expression on memory CTL

Virus-induced polyclonal B cell activation improves protective CTL memoryvia retained CD27 expression on memory CTL

Primary immune responses to human CMV: a critical role for IFN-γ–producing CD4+ T cells in protection against CMV disease

Cellular Immune Response of Fetuses to Cytomegalovirus

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