Tag: CD4

CD4 T lymphocytes from patients with chronic fatigue syndrome have decreased interferon-gamma production and increased sensitivity to dexamethasone

Abstract:

A disturbed hypothalamus-pituitary-adrenal gland axis and alterations at the immune system level have been observed in patients with chronic fatigue syndrome (CFS). Glucocorticoids are known to modulate T cell responses; therefore, purified CD4 T cells from CFS patients were studied to determine whether they have an altered sensitivity to dexamethasone (DEX).

CD4 T cells from CFS patients produced less interferon-gamma than did cells from controls; by contrast, interleukin-4 production and cell proliferation were comparable. With CD4 T cells from CFS patients (compared with cells from controls), a 10- to 20-fold lower DEX concentration was needed to achieve 50% inhibition of interleukin-4 production and proliferation, indicating an increased sensitivity to DEX in CFS patients.

Surprisingly, interferon-gamma production in patients and controls was equally sensitive to DEX. A differential sensitivity of cytokines or CD4 T cell subsets to glucocorticoids might explain an altered immunologic function in CFS patients.

 

Source: Visser J, Blauw B, Hinloopen B, Brommer E, de Kloet ER, Kluft C, Nagelkerken L. CD4 T lymphocytes from patients with chronic fatigue syndrome have decreased interferon-gamma production and increased sensitivity to dexamethasone. J Infect Dis. 1998 Feb;177(2):451-4. http://jid.oxfordjournals.org/content/177/2/451.long

 

Clinical improvement in chronic fatigue syndrome is not associated with lymphocyte subsets of function or activation

Abstract:

The relationship between markers of immune function and chronic fatigue syndrome (CFS) is controversial. To examine the relationship directly, 43 subjects with CFS entering a randomized controlled trial of a nonpharmacological treatment for CFS gave samples for immunological analysis before and after treatment. Percentage levels of total CD3+ T cells, CD4 T cells, CD8 T cells, and activated subsets did not differ between CFS subjects and controls. Naive (CD45RA+ RO-) and memory (CD45RA- RO+) T cells did not differ between subjects and controls.

Natural killer cells (CD16+/CD56+/CD3-) were significantly increased in CFS patients compared to controls, as was the percentage of CD11b+ CD8 cells.

There were no correlations between any immune variable and measures of clinical status, with the exception of a weak correlation between total CD4 T cells and fatigue. There was a positive correlation between memory CD4 and CD8 T cells and depression scores and a negative correlation between naive CD4 T cells and depression.

No immune measures changed during the course of the study, and there was no link between clinical improvement as a result of the treatment program and immune status. Immune measures did not predict response or lack of response to treatment.

In conclusion, we have been unable to replicate previous findings of immune activation in CFS and unable to find any important associations between clinical status, treatment response, and immunological status.

 

Source: Peakman M, Deale A, Field R, Mahalingam M, Wessely S. Clinical improvement in chronic fatigue syndrome is not associated with lymphocyte subsets of function or activation. Clin Immunol Immunopathol. 1997 Jan;82(1):83-91. http://www.ncbi.nlm.nih.gov/pubmed/9000046

 

Immunological abnormalities in patients with chronic fatigue syndrome

Abstract:

Between January 1991 and January 1993, 265 patients who fulfilled the CDC criteria of the working case definition of Chronic Fatigue Syndrome (CFS) have been observed at our Institution and submitted for clinical and laboratory evaluation.

One hundred and sixty-three patients were females and 102 males, the median age was 35 years (range 4-55 years); all patients reported profound and prolonged fatigue, lasting for a median of 3 years (range 6 months-10 years), preceded or accompanied at appearance by fever in 185 cases, and neuropsychologic problems including inability to concentrate, difficulty in thinking, confusion, irritability, forgetfulness, and depression. The fatigue was so severe that it required 102 patients to stop their working activities for a period of time ranging from 3 months to 2 years (range 7 months).

In 40 consecutive patients a comprehensive immunologic testing by single and two-colour flow cytometry was performed and results compared with a group of 35 healthy, age- and sex-matched controls. Whilst no significant differences were found in the absolute numbers of circulating total T cells (CD3+) and of total helper/inducer (CD4+) or suppressor/cytotoxic (CD8+) T cells, an evident reduction in CD3-/CD16+ and CD57+/CD56+ NK lymphocytes along with an expansion of the CD8+/CD56+ and CD16-/CD56+ NK subsets, were found in the CFS group.

In addition, CD56+ NK cells from CFS subjects were found to express an increased amount of cell adhesion molecules (CD11b, CD11c, CD54) and activation antigens (CD38). Both the percentage and absolute numbers of CD4+ T cells bearing the CD45RA antigen appeared significantly reduced in CFS patients, and CD4+ T lymphocytes from CFS subjects displayed an increased expression of the intercellular adhesion molecule-1 (ICAM-1/CD54).

Finally, the total numbers of circulating (CD19+) B lymphocytes, were significantly higher in CFS cases than in controls, and in 11 out of 30 CFS patients the increase in circulating B cells was sustained by the expansion of the CD5+/CD19+ subset of B lymphocytes.

We conclude that CFS is a syndrome not previously described in Italy, with already known clinical characteristics and appears to be associated with several immunologic abnormalities, including those reported previously in cohort of patients from different countries. We also show for the first time that CD56- NK cell subsets from CFS patients display an abnormally increased expression of cell adhesion molecules and activation markers.

 

Source: Tirelli U, Marotta G, Improta S, Pinto A. Immunological abnormalities in patients with chronic fatigue syndrome. Scand J Immunol. 1994 Dec;40(6):601-8. http://www.ncbi.nlm.nih.gov/pubmed/7997849

 

Biological and molecular characteristics of human herpesvirus 7: in vitro growth optimization and development of a syncytia inhibition test

Abstract:

Two isolates of human herpesvirus 7 (HHV-7) were recovered from phytohemagglutinin-activated peripheral blood mononuclear cells of a patient with chronic fatigue syndrome and of a healthy blood donor. A genetic polymorphism between the two isolates was detected by Southern blot analysis using a novel HHV-7 genomic clone (pVL8) as a probe. We developed optimized conditions for the in vitro propagation of HHV-7 by using enriched populations of activated CD4+ T lymphocytes derived from normal peripheral blood, resulting in the production of high-titered extracellular virus (> 10(6) cell culture infectious doses/ml). Bona fide syncytia formation was documented both in normal CD4+ T lymphocytes and in the Sup-T1 CD4+ T-cell line following infection with high-titered HHV-7. To identify neutralizing antibodies to HHV-7, a syncytia-inhibition test was developed. Variable titers of syncytia-neutralizing antibodies were detected in all the human sera tested, thus confirming the high prevalence of HHV-7 in the human population.

 

Source: Secchiero P, Berneman ZN, Gallo RC, Lusso P. Biological and molecular characteristics of human herpesvirus 7: in vitro growth optimization and development of a syncytia inhibition test. Virology. 1994 Jul;202(1):506-12. http://www.ncbi.nlm.nih.gov/pubmed/8009865

 

Infection of natural killer cells by human herpesvirus 6

Abstract:

Natural killer (NK) cells are a functionally defined subset of non-T, non-B lymphocytes of bone marrow origin, which induce lysis of selected target cells, including neoplastic and virus-infected cells. The NK cell function provides an important mechanism of primary defence against viruses in vivo, as demonstrated by the occurrence of multiple herpesvirus infections in patients congenitally lacking NK cells.

Here we show that functionally competent CD3- NK clones can be productively infected by human herpesvirus 6 (HHV-6), a T-lymphotropic DNA virus that may play a role in the acquired immunodeficiency syndrome (AIDS) and in the chronic fatigue syndrome, two disorders associated with a defective NK cell activity.

The infection is cytopathic and induces de novo expression of CD4, an antigen not expressed within the NK lineage, thereby predisposing NK cells to infection by human immunodeficiency virus type 1 (HIV-1).

These results provide evidence that a herpesvirus can directly target and kill NK cells, a potential strategy to suppress the natural anti-viral immunity of the host.

 

Source: Lusso P, Malnati MS, Garzino-Demo A, Crowley RW, Long EO, Gallo RC. Infection of natural killer cells by human herpesvirus 6. Nature. 1993 Apr 1;362(6419):458-62. http://www.ncbi.nlm.nih.gov/pubmed/7681936

 

Lymphocyte phenotype and function in the chronic fatigue syndrome

Abstract:

Lymphocytes of 18 patients meeting the Centers for Disease Control (CDC) case definition for the chronic fatigue syndrome (CFS), 10 similar, chronically fatigued patients not fully conforming to the CDC case definition, and 17 matched, healthy individuals were studied to determine the presence of abnormalities of peripheral cell phenotype and function.

Extensive phenotypic analyses of B- and T-cell subsets, natural killer (NK) cells, and macrophages were performed using single-, dual-, and three-color flow cytometry. Compared to controls, in CFS patients the percentage of CD4 T cells and CD4,CD45RA, or naive T cells, was reduced. The CD4,CD45RO, or memory T-cell, subset was numerically normal but expressed increased levels of adhesion markers (CD29, CD54, and CD58). CFS patient lymphocytes showed reduced proliferative responses to phytohemagglutinin, concanavalin A, and staphylococcal enterotoxin B. Lymphocytes from fatigue patients not meeting the CDC definition showed similar abnormalities.

These data indicate that peripheral T cells manifest an increased state of differentiation in CFS and related conditions. This may arise as a consequence of an underlying neuropsychiatric and/or neuroendocrine disorder or because of exposure to antigens or superantigens of an infectious agent.

 

Source: Straus SE, Fritz S, Dale JK, Gould B, Strober W. Lymphocyte phenotype and function in the chronic fatigue syndrome. J Clin Immunol. 1993 Jan;13(1):30-40. http://www.ncbi.nlm.nih.gov/pubmed/8095270

 

Human herpesvirus-6 (HHV-6) (short review)

Abstract:

Human Herpesvirus-6 is the etiological agent of Roseola infantum and approximately 12% of heterophile antibody negative infectious mononucleosis. HHV-6 is T-lymphotropic, and readily infects and lyses CD4+ cells. The prevalence rate of HHV-6 in the general population is about 80% (as measured by IFA) with an IgG antibody titer of 1:80. A lower prevalence, however, is observed in some countries.

HHV-6 is reactivated in various malignant and non-malignant diseases as well as in Chronic Fatigue Syndrome and transplant patients. Furthermore, elevated antibody titers were also observed in lymphoproliferative disorders, auto-immune diseases and HIV-1 positive AIDS patients. There appears to be some strain variability in HHV-6 isolates.

The GS isolates of HHV-6 (prototype) was resistant to Acyclovir, Gancyclovir, but its replication was inhibited by Phosphonoacetic acid and Phosphoformic acid. HHV-7 isolated from healthy individuals showed, by restriction analysis, that 6 out of 11 probes derived from two strains of HHV-6, cross-hybridized with DNA fragments, derived from HHV-7.

 

Source: Ablashi DV, Salahuddin SZ, Josephs SF, Balachandran N, Krueger GR, Gallo RC. Human herpesvirus-6 (HHV-6) (short review). In Vivo. 1991 May-Jun;5(3):193-9. http://www.ncbi.nlm.nih.gov/pubmed/1654146

 

What’s new in human herpesvirus-6? Clinical immunopathology of the HHV-6 infection

Abstract:

Human herpesvirus-6 (HHV-6), formerly known as human B-lymphotropic virus (HBLV), was first isolated in 1986 from patients with lymphoproliferative disorders and AIDS. Antibody prevalence against HHV-6 varies between about 60-80% indicating a widespread latent infection.

Although HHV-6 infects in vivo primarily T-lymphocytes, it is associated with similar diseases as in infection with Epstein-Barr virus (EBV), a clearly B-lymphotropic virus. Reactivation of latent HHV-6 infection in patients with subnormal host defense may cause persistent active infection with so-called postinfectious chronic fatigue syndrome (PICFS) or may contribute to other pathologies such as immune deficiency itself, autoimmune disorders or progressive lymphoproliferation.

Coinfection of CD4 cells by HHV-6 and human immunodeficiency virus (HIV 1) in AIDS patients can aggravate HIV-induced acquired immune deficiency. These characteristics of the only recently detected new virus justify further intense investigation.

 

Source: Krueger GR, Sander C.  What’s new in human herpesvirus-6? Clinical immunopathology of the HHV-6 infection. Pathol Res Pract. 1989 Dec;185(6):915-29. http://www.ncbi.nlm.nih.gov/pubmed/2559396

 

Immunological abnormalities in the chronic fatigue syndrome

Abstract:

The chronic fatigue syndrome is a disorder of unknown aetiology which is characterized by debilitating fatigue. Recent evidence has suggested that viruses may persist in the tissues of patients with chronic fatigue syndrome. A concurrent immunological disturbance is likely to be associated with the persistence of viral antigens.

Therefore, the humoral and cellular immunity of 100 patients who were suffering from chronic fatigue syndrome and that of 100 healthy, age- and sex-matched control subjects were compared. This study documents the frequent occurrence of abnormalities within the cellular and humoral immune systems of patients with well-defined chronic fatigue syndrome. Disordered immunity may be central to the pathogenesis of chronic fatigue syndrome.

In patients with chronic fatigue syndrome, a significant (P less than 0.01) reduction was found in the absolute number of peripheral blood lymphocytes in the total T-cell (CD2), the helper/inducer T-cell (CD4) and the suppressor/cytotoxic T-cell (CD8) subsets. A significant (P less than 0.001) reduction also was found in T-cell function, which was measured: in vivo by delayed-type hypersensitivity skin-testing (reduced responses were recorded in 50 [88%] of 57 patients); and in vitro by phytohaemagglutinin stimulation. Reduced immunoglobulin (Ig) levels were common (56% of patients), with the levels of serum IgG3- and IgG1-subclasses particularly (P less than 0.05) affected.

 

Source: Lloyd AR, Wakefield D, Boughton CR, Dwyer JM. Immunological abnormalities in the chronic fatigue syndrome. Med J Aust. 1989 Aug 7;151(3):122-4. http://www.ncbi.nlm.nih.gov/pubmed/2787888