A Decrease of Regulatory T Cells and Altered Expression of NK Receptors Are Observed in Subacute Sclerosing Panencephalitis

Abstract

Subacute sclerosing panencephalitis (SSPE) is caused by a persistent measles virus infection. Regulatory mechanisms can be responsible for a failure of immunosurveillance in children with SSPE. In this study, peripheral blood cells of 71 patients with SSPE and 57 children with other diseases were compared phenotypically. The proportions of CD4⁺, CD8⁺ T, and NK cells were homogenous, whereas total CD3⁺ T and Treg (CD4⁺CD25⁺CD152⁺) cells were decreased in patients with SSPE. The proportion of CD8⁺ T cells expressing the inhibitory NKG2A⁺ receptor was also decreased (1.7%±1.7% vs. 2.6%±1.9%, p=0.007) in patients with SSPE, whereas the proportion of NK cells expressing activating NKG2C was increased compared with the control group (30.0%±17.3% vs. 22.2%±17.0%, p=0.039). The decrease in the number of cells with regulatory phenotype, the lower presence of the inhibitory NK receptors on CD8⁺ cells, and higher activating NK receptors on NK cells in SSPE indicate an upregulation of these cell types that favors their response. This state of active immune response may be caused by chronic stimulation of viral antigens leading to altered regulatory pathways.

Introduction

Subacute sclerosing panencephalitis (SSPE) is a rare but fatal disorder of the central nervous system (CNS) caused by measles virus (MV) infection. Despite the long interval between the acute infection and symptoms of SSPE, evidence supports that MV infection of the brain occurs soon after the acute infection. High levels of anti-MV antibodies are present in the serum and cerebrospinal fluid (CSF) of patients with SSPE (11,16). The cause of persistence and the pathogenesis of SSPE is still unresolved and both viral and host factors seem to be involved (9,13). Since the introduction of an effective measles vaccine, the incidence of 1 per 1 million children a year has declined substantially (10). However, in a surveillance study, the incidence of SSPE in Istanbul is still reported as 2 per 1 million (24). Recent findings support that there are no particular neurovirulent MV genotypes circulating and that persistent brain infections are established by a normal wild-type MV strain (26). Slow clearance after apparent recovery has been suggested as the explanation for a prolonged presence of MV RNA (15). An immature immune response with the transient immunosuppression by the MV may establish the persistence of the viral infection. A switch of T-cell response from type 1 to type 2 with production of regulatory T cells (Tregs) and cytokines may cause slow clearance of viral RNA (36). Several persistent viruses induce Tregs that subvert protective immune mechanisms and promote viral persistence (7,34). Considering SSPE as a failure of immune response, regulatory mechanisms may play a role in susceptible children. Among various types of Tregs, naturally occurring CD4⁺CD25⁺ Tregs that arise within the thymus express high levels of the α-chain of the interleukin-2 receptor (CD25). Although Tregs do not have a unique phenotype, the presence of a combination of CD25, cytotoxic T lymphocyte-associated antigen 4 (CTLA-4, CD152), glucocorticoid-induced tumor necrosis factor receptor (GITR), and FOXP3 is frequently used for their identification (3). Supporting a role in SSPE, CD4⁺CD25⁺FoxP3⁺ regulatory T cells are enriched following MV infection, both in the periphery and in the brain (29).

On the other hand, the effect of inhibitory/activating NK receptors (NKR) on effector cells may also be operating in virus-specific CD8⁺ T cells or NK cells, which can be controlled by variable expression of their ligands during viral infection. NKR expressed on antiviral cells can control cytotoxic and cytokine-producing activities of T and NK cells (18). Among NKR, binding of heterodimers of CD94 to its ligand conveys an inhibitory signal when with NKG2A, whereas the signal through CD94/NKG2C has a costimulatory effect (2). CD94/NKG2A and CD94/NKG2C are normally expressed on most NK cells and on a small fraction of CD8⁺ T lymphocytes (20,37). Inhibitory NKR can differentially regulate the activities of CD8⁺ T cells, which protect against viruses that are completely cleared compared with those that establish persistent infection (21).

For the identification of the immune mechanisms required for the reactivation of the persistent MV, we analyzed probable Tregs and the expression of regulatory molecules on T and NK cells in SSPE patients.

Materials and Methods

Patients and controls

Seventy-one patients with SSPE (45 boys and 26 girls, mean age: 10±6 years) were recruited for the study between the years 2002 and 2013. All patients had increased anti-MV antibody titers and oligoclonal IgG bands in CSF, with typical electroencephalographic and clinical features fulfilling the criteria for SSPE (12,13,25). According to the clinical staging, 10 patients had early findings (1 patient with 1B and 9 patients with 2A) and 32 patients had more severe disease at 2B (n=12), 2C (n=14), 2D (n=3), 2 (n=3), and 4 (n=1) stages. Fifty patients had natural measles between the ages of 3 months and 9 years. The measles history of the remaining 17 patients was unknown. Thirty-seven of the patients had a history of measles vaccination. Informed consent was obtained from the parents, and the Ethics Committee approval was taken locally.

Fifty-seven children (23 girls and 34 boys, mean age: 9±6 years) were used as controls (CON). Twenty-eight (mean age: 9±4 years) had inflammatory diseases (inflammatory controls [ICON]) such as upper respiratory tract infections, asthma, and otitis media, and 29 (mean age: 10±7 years) had noninflammatory diseases like epilepsy and Lafora (non-inflammatory controls [NICON]) or no specified symptoms. Due to the ethical considerations of taking blood from healthy children, we could not include healthy donors.

Phenotypic staining and reagents

Erythrocyte-lysed peripheral blood cells of donors were surface stained with fluorochrome-conjugated mouse anti-human CD3-APC, CD8-APC, CD4-APC, CD25-FITC (all IgG1; DakoCytomation, Glostrup, Denmark), CD56-FITC (IgG2a; Serotec, Oxford, United Kingdom), CD152-PE (anti-CTLA-4, IgG2a), CD94-FITC (IgG1), CD28-PE (IgG1; BD Biosciences Pharmingen, Erembodegem, Belgium), NKG2A-PE (IgG2a), NKG2C-PE (IgG1; R&D Systems, Minneapolis, MN), CD45-FITC/CD14-PE (IgG1/IgG2a; Diaclone, Stanford, CT) antibodies, and isotype control antibodies (BD Biosciences Pharmingen, DakoCytomation, Glostrup, Denmark). Cell subset phenotypes were analyzed by flow cytometry (FACSCalibur; Becton-Dickinson) and compared in both lymphocyte (CD45⁺CD14⁻) and respective cell-type gates (CD8⁺, CD4⁺, CD56⁺) between groups (Supplementary Fig. S1; Supplementary Data are available online at www.liebertpub.com/vim).

Statistical analyses

Statistical analyses were performed by the nonparametric Mann–Whitney U test for comparisons. Results are presented as mean values. As no significant difference was detected between the ICON and NICON groups, we evaluated all control donors as a single CON group.

Results

Distribution of T and NK cells in the blood

To determine the proportions of CD3⁺, CD4⁺, CD8⁺, and CD8⁻CD56⁺ cells in patients with SSPE and CON, lymphocyte gate (CD45⁺CD14⁻) was applied. The proportion of CD3⁺ T cells was slightly decreased in patients with SSPE compared with age-matched CON (60.9%±12.8% vs. 66.1%±11.4%, p=0.028). The lower percentage of CD3⁺ cells in patients with SSPE could not have been caused by an altered ratio of CD4⁺ or CD8⁺ cells because no statistically significant difference was observed in CD4⁺ and CD8⁺ T cells between the groups (33.9%±11.4% vs. 33.4%±10.8% and 27.5%±8.7% vs. 26.2%±8.6%, respectively). When the distribution of CD8⁻CD56⁺ NK cells was compared, the proportions were similar in both groups (6.0%±5.1% vs. 6.1%±4.7%, Fig. 1).

FIG. 1.

The proportions of CD3⁺, CD4⁺, CD8⁺ T cells and CD8⁻CD56⁺ NK cells in subacute sclerosing panencephalitis (SSPE) and CON donors. CD3⁺ T cells are slightly decreased in SSPE patients compared to CON. Results are presented with mean (horizontal lines)±SD values. Black circles, SSPE donors; black triangles, CON donors.

Regulatory T cells in SSPE patients

As possible regulatory cells, we analyzed CD4⁺CD25^high, CD4⁺CD152⁺ cells, and the suppressor phenotype CD8⁺CD28⁻ cells. The proportion of most probable Tregs, CD4⁺CD25^high cells, was lower in patients with SSPE than CON (1.0%±4.1% vs. 1.6%±2.8%, p=0.043, Fig. 2A). When Tregs were identified as CD152⁺ on CD4⁺CD25⁺ cells, the proportion of these cells in lymphocytes was lower in the SSPE group compared with CON, with a tendency to differ (2.0%±2.7% vs. 4.0%±3.7%, p=0.051, Fig. 2B). CD4⁺CD152⁺ cells were also downregulated in patients with SSPE compared with CON (0.6%±0.7% vs. 1.1%±0.8%, p=0.003, Fig. 2C). The distribution of CD8⁺CD28⁻ cells was not different between groups (data not shown).

FIG. 2.

Proportions of regulatory T cells (Tregs) in SSPE patients and CON. The distribution in groups and mean (horizontal lines)±SD values are presented. (A) The proportion of CD4⁺ CD25^high Tregs cells is lower in SSPE patients than CON. (B) CD4⁺CD25⁺CD152⁺T cells were also decreased in the SSPE group compared to CON. (C) The group of CD4⁺CD152⁺ cells was downmodulated in SSPE patients compared to CON. Black circles, SSPE donors; black triangles, CON donors.

Regulatory receptor expression on NK cells

To investigate the expression of heterodimeric inhibitory NKG2A or activating NKG2C receptors in patients with SSPE, we compared the presence of these molecules on NK cells. The presence of inhibitory NKG2A molecules on CD8⁻CD56⁺ NK cells as well as CD56⁺NKG2A⁺ double-positive cells among the lymphocytes was not different in the SSPE and CON groups (27.5%±21% vs. 29.6%±20% and 2.4%±2% vs. 3.5%±3%, respectively, Fig. 3A). Although the CD56⁺NKG2C⁺ double-positive cells were relatively low in both groups (2.3%±1.7% vs. 2.4%±2.3%), the expression of the activating NKG2C on CD56⁺CD8⁻ cells was higher in patients with SSPE compared with CON (30.0%±17% vs. 22.2%±17%; p=0.039, Fig. 3B).

FIG. 3.

Analysis of NKG2A and NKG2C expression on CD8^−-CD56⁺ NK cells in the SSPE and CON groups. Mean (horizontal lines)±SD values are presented. (A) Inhibitory NKG2A receptor on NK cells. (B) Activating NKG2C receptor was upregulated on NK cells in SSPE patients compared to CON. Black circles, SSPE donors; black triangles, CON donors.

Regulatory receptor expression on CD8⁺ T cells

Next, we analyzed the expression of the same NKR on CD8⁺ T cells. Although the proportions of CD8⁺ T cells were not different between the groups, the percentage of CD8⁺CD94⁺ cells in lymphocytes was lower in patients with SSPE than in CON (4.3%±2% vs. 5.9%±3%; p=0.056). This cell group was further evaluated for the receptors with activating or inhibitory heterodimers. The proportion of CD8⁺ cells expressing the inhibitory NKG2A was lower in patients with SSPE than in the CON group (1.7%±1.7% vs. 2.6%±1.9%; p=0.007, Fig. 4A), whereas CD8⁺ cells expressing the activating NKG2C were not different between groups (3.1%±3.0% vs. 3.2%±3.0%, Fig. 4B).

FIG. 4.

The expression of NKG2A and NKG2C on CD8⁺ cytotoxic T cells. Mean (horizontal lines)±SD values are presented. (A) In SSPE patients, the CD8⁺NKG2A⁺cell frequency was lower than the CON group. (B) No significant difference in the CD8⁺NKG2C⁺ cells between groups is observed. Black circles, SSPE donors; black triangles, CON donors.

A positive correlation between CD8⁺CD94⁺ cells and CD8⁺NKG2A⁺ cells was observed only in the CON (r=0.46, p=0.006) and not present in SSPE, which implicated a dysregulation of these surface molecules in SSPE. CD8⁺CD94⁺ and CD8⁺NKG2C⁺ cells were correlated in both the SSPE and CON groups (r=0.59, p=0.001 and r=0.41, p=0.02, respectively).

Discussion

To characterize the general state of the immune system during the persistent MV infection, we analyzed the regulatory cells and molecules with regulatory function on the blood cells in SSPE. By comparing the patients with SSPE with controls, we noted a decrease in the number of cells with regulatory phenotype and an increase of activating receptors on NK cells but not on CD8⁺ cells, which indicated alterations in both cell types.

Previous studies in SSPE revealed lower proportions of CD3⁺ T cells (27), but increased percentage of CD8⁺ T and NK cells (1,31). In this relatively large cohort of patients with SSPE, the decrease of CD3⁺ T cells was replicated, whereas the total NK and CD8 cells were not increased. The decrease in the number of CD3⁺ cells may be caused by MV-infected monocyte-induced apoptosis of these cells (33).

Measles is a highly contagious childhood disease that is associated with a strong virus-specific immune response resulting with the establishment of lifelong immunity. Measles infection is also followed by an acute and profound immunosuppression leading to an increased susceptibility to secondary infections (14). The immunosuppression observed after the acute infection may also be a possible link to viral persistence that causes late disease forms such as SSPE. However, our findings indicate that no suppression by Tregs is evident during the clinical chronic phase of established disease.

Along with CD25 and FOXP3, the CD4⁺ regulatory T-cell population requires CTLA-4 as a costimulatory molecule for stronger functional activation (4,30). Due to the limited volumes of blood available from these rare disease patients, surface staining only is preferred for the identification of Tregs cells and no functional evaluation was possible. The increase of CD4⁺CD25⁺ Tregs has been demonstrated in adults as well as in animal models in the acute phase of an MV infection (28,36). Despite the increased frequency of FOXP3⁺CD25⁺CD4⁺ Tregs both in the periphery and in the brain, specific antiviral responses could be demonstrated, whereas the capability of T lymphocytes to respond to virus-unrelated antigens was strongly suppressed. This finding implicated that MV affects regulatory T-cell homeostasis and that MV-induced Tregs could have favored the development of persistence and SSPE (29). However, in a persistent MV infection model, depletion of CD4⁺CD25⁺FOXP3⁺ Tregs increased virus-specific CD8⁺ effector T cells in the brain and caused a reduction of the persistent infection (26). Viral persistence was also shown to be relatively independent of CD25⁺CD4⁺ Tregs in another recent model of acute viral infection (8). The present results do not provide evidence for the effect of CD4⁺CD25^high Tregs in the persistent brain disease stage. Lower numbers of CD4⁺CD25^high T cells in the patients with SSPE may be related to the late time point of the disease and a compensatory mechanism induced by viral persistence for a more efficient viral clearance.

Expression of NKR on NK and CD8⁺ T cells, which may be involved in the cellular responses in SSPE, was also investigated in this study. NK cells may respond to persistent virus by expressing the activating receptor NKG2C, proliferate, and maintain in numbers for a prolonged period of time dependent on virus-induced ligands (17). Human cytomegalovirus and human immunodeficiency virus (HIV) infections are associated with increased percentages of a particular NK cell subset expressing the activating receptor CD94/NKG2C (23,32). In SSPE, the relative increase of activating NKG2C on NK cells in the periphery may also represent the continuous but inefficient activity during a sustained viral infection.

CD8⁺ T lymphocytes mediate immunosurveillance against persistent virus infections. NKR-expressing CD94/NKG2⁺CD8⁺ T cells are oligoclonal populations characterized by an effector memory phenotype, suggesting that they could be the result of antigen-specific expansion in vivo (5). However, pathogen-specific CD8⁺ T cells may also initiate expression of the inhibitory CD94/NKG2A upon activation and this expression maintains long term in persistent infections by repeated TCR stimulation (6,19). The percentage of CD8⁺ T lymphocytes expressing the inhibitory heterodimer was shown to be significantly decreased in HIV-I-infected patients in comparison with noninfected controls, with no significant difference in activating CD94/NKG2C⁺ on CD8⁺ (37). A similar decrease of NKG2A on CD8⁺ with the accompanying increase of NKG2C on NK cells was recently demonstrated in an HIV infection with a higher viral load (32). Our results revealed close similarities to the HIV infection. No evidence for a mechanism of immunosuppression by either NK or CD8⁺ T cells is supported in SSPE by the present findings.

An increase of activating receptor on NK and the decrease of inhibiting receptor on cytotoxic T cells in SSPE favor an immune status where the antiviral response is probably facilitated through both cell groups, although it has not been sufficient to clear the virus efficiently. Our data cannot determine whether this is a result of high viral load or of sequestration of the specific cells into the CNS. Our results implicate that the downregulation of the inhibitory NKR NKG2A on CD8⁺ cells in SSPE may be caused by altered regulation of CD8⁺ T cells. Inhibitory NKG2A receptors may induce MV-specific CD8⁺ T-cell population to become cytolitically anergic, which may have contributed to virus persistence. This finding is also in accordance with our previous data on inefficient T-cell responses in patients with SSPE. These children may produce only an exhausted immune response, which causes viral persistence due to inefficient removal of the virus (35).

The findings of the present study may only reflect the cell distribution in the peripheral blood, and the possibility of an accumulation of the regulatory cell groups in the CNS cannot be excluded by the data in SSPE (22). A better understanding of the balance between measles-induced effector and regulatory mechanisms, both in the periphery and in the brain, may be of critical importance in the design of novel approaches for the prevention and treatment of measles pathology. Further investigations of T-cell functions of SSPE patients will elucidate the pathogenic mechanisms in this disease.

Footnotes

Acknowledgments

The authors thank the physicians who follow patients with SSPE, for referring their patients. Also, the critical reading by David Chapman is appreciated. The study is supported by grants from the Research Fund of Istanbul University (Project #: 192).

Author Disclosure Statement

No competing financial interests exist.

References

Anlar

, Guven

, Kose

, et al. Lymphocyte subsets, TNF alpha and interleukin-4 levels in treated and untreated subacute sclerosing panencephalitis patients. J Neuroimmunol, 2005; 163:195–198.

Arlettaz

, Villard

, de Rham

, et al. Activating CD94:NKG2C and inhibitory CD94:NKG2A receptors are expressed by distinct subsets of committed CD8+ TCR alphabeta lymphocytes. Eur J Immunol, 2004; 34:3456–3464.

Becker

, Stoll

, Bopp

, et al. Regulatory T cells: present facts and future hopes. Med Microbiol Immunol, 2006; 195:113–124.

Birebent

, Lorho

, Lechartier

, et al. Suppressive properties of human CD4+CD25+ regulatory T cells are dependent on CTLA-4 expression. Eur J Immunol, 2004; 34:3485–3496.

Braud

, Aldemir

, Breart

, and Ferlin

. Expression of CD94-NKG2A inhibitory receptor is restricted to a subset of CD8+ T cells. Trends Immunol, 2003; 24:162–164.

Byers

, Andrews

, and Lukacher

. CD94/NKG2A expression is associated with proliferative potential of CD8 T cells during persistent polyoma virus infection. J Immunol, 2006; 176:6121–6129.

Card

, McLaren

, Wachihi

, et al. Decreased immune activation in resistance to HIV-1 infection is associated with an elevated frequency of CD4+CD25+FOXP3+regulatory T cells. J Infect Dis, 2009; 199:1318–1322.

de Aquino

, Puntambekar

, Savarin

, et al. Role of CD25(+) CD4(+) T cells in acute and persistent coronavirus infection of the central nervous system. Virology, 2013; 447:112–120.

Dyken

. Neuroprogressive disease of post-infectious origin: a review of a resurging subacute sclerosing panencephalitis (SSPE). Ment Retard Dev Disabil Res Rev, 2001; 7:217–225.

10.

Garg

. Subacute sclerosing panencephalitis. Postgrad Med J, 2002; 78:63–70.

11.

Garg

. Subacute sclerosing panencephalitis. J Neurol, 2008; 255:1861–1871.

12.

Gascon

. Subacute sclerosing panencephalitis. Semin Pediatr Neurol, 1996; 3:260–269.

13.

Graves

. Subacute sclerosing panencephalitis. Neurol Clin, 1984; 2:267–280.

14.

Griffin

. Measles virus-induced suppression of immune responses. Immunol Rev, 2011; 236:176–189.

15.

Griffin

, Lin

, and Pan

. Measles virus, immune control, and persistence. FEMS Microbiol Rev, 2012; 36:649–662.

16.

Hara

, Yamashita

, Aiba

, et al. Measles virus-specific T helper 1/T helper 2-cytokine production in subacute sclerosing panencephalitis. J Neurovirol, 2000; 6:121–126.

17.

Lee

, and Biron

. Here today—not gone tomorrow: roles for activating receptors in sustaining NK cells during viral infections. Eur J Immunol, 2010; 40:923–932.

18.

McMahon

, and Raulet

. Expression and function of NK cell receptors in CD8+ T cells. Curr Opin Immunol, 2001; 13:465–470.

19.

McMahon

, Zajac

, Jamieson

, et al. Viral and bacterial infections induce expression of multiple NK cell receptors in responding CD8(+) T cells. J Immunol, 2002; 169:1444–1452.

20.

Mingari

, Pietra

, and Moretta

. Human cytolytic T lymphocytes expressing HLA class-I-specific inhibitory receptors. Curr Opin Immunol, 2005; 17:312–319.

21.

Moser

, Byers

, and Lukacher

. NK cell receptors in antiviral immunity. Curr Opin Immunol, 2002; 14:509–516.

22.

Nattermann

, Sherzada

, Iwan

, et al. Hepatitis C virus-induced secretion of inflammatory chemokines preferentially recruits NKG2A+CD8+ T cells. J Infect Dis, 2008; 198:213–217.

23.

Noyola

, Fortuny

, Muntasell

, et al. Influence of congenital human cytomegalovirus infection and the NKG2C genotype on NK-cell subset distribution in children. Eur J Immunol, 2012; 42:3256–3266.

24.

Onal

, Gurses

, Direskeneli

, et al. Subacute sclerosing panencephalitis surveillance study in Istanbul. Brain Dev, 2006; 28:183–189.

25.

Ozturk

, Gurses

, Baykan

, et al. Subacute sclerosing panencephalitis: clinical and magnetic resonance imaging evaluation of 36 patients. J Child Neurol, 2002; 17:25–29.

26.

Reuter

, Sparwasser

, Hunig

, and Schneider-Schaulies

. Foxp3+ regulatory T cells control persistence of viral CNS infection. PLoS One, 2012; 7:e33989.

27.

Sanal

, Basaran

, Aysun

, et al. Subpopulations of T lymphocytes in subacute sclerosing panencephalitis (SSPE). Turk J Pediatr, 1986; 28:23–29.

28.

Sellin

, and Horvat

. Current animal models: transgenic animal models for the study of measles pathogenesis. Curr Top Microbiol Immunol, 2009; 330:111–127.

29.

Sellin

, Jegou

J-F

, Renneson

, et al. Interplay between virus-specific effector response and Foxp3+regulatory T cells in measles virus immunopathogenesis. PLoS One, 2009; 4:e4948.

30.

Takahashi

, Tagami

, Yamazaki

, et al. Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J Exp Med, 2000; 192:303–310.

31.

Tekgul

, Tutuncuoglu

, Kutukculer

, et al. Lymphocyte subsets and inflammatory mediators in patients with subacute sclerosing panencephalitis. J Child Neurol, 1999; 14:418–421.

32.

Thomas

, Low

, Kniesch

, et al. NKG2C deletion is a risk factor of HIV infection. AIDS Res Hum Retroviruses, 2012; 28:844–851.

33.

Vuorinen

, Peri

, and Vainionpää

. Measles virus induces apoptosis in uninfected bystander T cells and leads to granzyme B and caspase activation in peripheral blood mononuclear cell cultures. Eur J Clin Invest, 2003; 33:434–442.

34.

Wingate

, McAulay

, Anthony

, and Crawford

. Regulatory T cell activity in primary and persistent Epstein–Barr virus infection. J Med Virol, 2009; 81:870–877.

35.

Yentur

, Gurses

, Demirbilek

, et al. Alterations in cell-mediated immune response in subacute sclerosing panencephalitis. J Neuroimmunol, 2005; 170:179–185.

36.

, Cheng

, Shi

, et al. Measles virus infection in adults induces production of IL-10 and is associated with increased CD4+ CD25+ regulatory T cells. J Immunol, 2008; 181:7356–7366.

37.

Zeddou

, Rahmouni

, Vandamme

, et al. Downregulation of CD94/NKG2A inhibitory receptors on CD8+ T cells in HIV infection is more pronounced in subjects with detected viral load than in their aviraemic counterparts. Retrovirology, 2007; 4:72.

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A Decrease of Regulatory T Cells and Altered Expression of NK Receptors Are Observed in Subacute Sclerosing Panencephalitis

Abstract

Introduction

Materials and Methods

Patients and controls

Phenotypic staining and reagents

Statistical analyses

Results

Distribution of T and NK cells in the blood

Regulatory T cells in SSPE patients

Regulatory receptor expression on NK cells

Regulatory receptor expression on CD8+ T cells

Discussion

Footnotes

Acknowledgments

Author Disclosure Statement

References

Supplementary Material

Regulatory receptor expression on CD8⁺ T cells