Tag: NK cell function

A Comparison of Immune Functionality in Viral versus Non-Viral CFS Subtypes

Abstract:

Participants with CFS were grouped into viral and non-viral onset fatigue categories and assessed for differential immunological marker expression. Peripheral Blood Mononuclear Cells were assessed for differential phenotypic expression of surface adherence glycoproteins on circulating lymphocytes. The flow cytometric analysis employed fluorescent monoclonal antibody labeling.

The viral in comparison to the non-viral group demonstrated significant elevations in several Th1 type subsets including: the percentage and number of CD4+ cells, the percentage and number of CD2+CD26+ cells, the percentage and number of CD2+CD4+CD26+ cells, the percentage and number of CD4+ CD26+ cells, and the percentage of Th2 naïve cells (CD4+ CD45RA+CD62L+).

Of the remaining significant findings, the non viral group demonstrated significant elevations in comparison to the viral group for the following Th1 type subsets: the percentage of CD8+ cells, the percentage of T-cytotoxic suppressor cells (CD3+8+), and the percentage and number of Th1 memory cells (CD8+CD45RA-CD62L-).

The viral group demonstrated a pattern of activation that differed from that of the group with a non-viral etiology, as evidenced by an elevated and out of range percentage and number of CD4+ cells, the percentage of CD2+CD26+, and the percentage of Th2 naïve cells (CD4+CD45RA+CD62L+). Both groups demonstrated reduced and out of range Natural Killer Cell Cytotoxicity and percentage of B-1 cells (CD5+CD19).

In addition, both groups demonstrated an elevated and out of range percentage of CD2+CD8+CD26+, percentage of the Th1 memory subset (CD4+CD45RA-CD62L-), the percentage of Th1 memory and naïve cells (CD8+CD45RA-CD62L-, CD8+CD45RA+CD62L-), the percentage and number of Th2 memory cells (CD4+CD45RA-CD62L+), and the percentage of Th2 memory and naïve cells (CD8+CD45RA-CD62L+, CD8+CD45RA+CD62L+).

These findings imply that the homeostatic mechanism responsible for the regulation of the Th1 (cell mediated) and Th2 (humoral) immune responses is disturbed in CFS. The implications of these findings are discussed.

 

Source: Porter N, Lerch A, Jason LA, Sorenson M, Fletcher MA, Herrington J. A Comparison of Immune Functionality in Viral versus Non-Viral CFS Subtypes. J Behav Neurosci Res. 2010 Jun 1;8(2):1-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951052/ (Full article)

 

Chronic fatigue syndrome is associated with diminished intracellular perforin

Abstract:

Chronic fatigue syndrome (CFS) is an illness characterized by unexplained and prolonged fatigue that is often accompanied by abnormalities of immune, endocrine and cognitive functions. Diminished natural killer cell cytotoxicity (NKCC) is a frequently reported finding. However, the molecular basis of this defect of in vitro cytotoxicy has not been described.

Perforin is a protein found within intracellular granules of NK and cytotoxic T cells and is a key factor in the lytic processes mediated by these cells. Quantitative fluorescence flow cytometry was used to the intracellular perforin content in CFS subjects and healthy controls.

A significant reduction in the NK cell associated perforin levels in samples from CFS patients, compared to healthy controls, was observed. There was also an indication of a reduced perforin level within the cytotoxic T cells of CFS subjects, providing the first evidence, to our knowledge, to suggest a T cell associated cytotoxic deficit in CFS. Because perforin is important in immune surveillance and homeostasis of the immune system, its deficiency may prove to be an important factor in the pathogenesis of CFS and its analysis may prove useful as a biomarker in the study of CFS.

 

Source: Maher KJ, Klimas NG, Fletcher MA. Chronic fatigue syndrome is associated with diminished intracellular perforin. Clin Exp Immunol. 2005 Dec;142(3):505-11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1440524/ (Full article)

 

Predictive immunophenotypes: disease-related profile in chronic fatigue syndrome

Abstract:

BACKGROUND: There is a growing body of evidence supporting the theory that problems with immune function play an important role in chronic fatigue syndrome (CFS).

METHODS: We studied 90 CFS cases and 50 healthy controls from two different areas of upstate New York to determine whether there were differences in the absolute number and pattern of natural killer (NK) and cytotoxic T-cell phenotypes between CFS cases and healthy controls in the two regions. One group was from a small town where a cluster of cases existed; the other was from a large metropolitan area where there was not a known cluster.

RESULTS: The number of CD56+CD3+CD8+ and CD56+CD3+CD8- cells in cases from the two areas were both significantly elevated over that of controls from the metropolitan area (P < 0.03). The number of CD56+CD3-CD8+ and CD56+CD3-CD8- cells was significantly reduced in the two case groups compared to that of controls from the metropolitan area (P = 0.04). However, controls who were from the same town as the cluster cases had numbers of CD56+CD3+CD8+, CD56+CD3+CD8-, and CD56+CD3-CD8- cells that were more like that of cases than controls. Only the number of CD56+CD3-CD8+ cells (an NK cell subset) was significantly different in cases versus controls from the cluster area (P = 0.022).

CONCLUSIONS: These data suggest that differences in controls from cluster and noncluster areas may be responsible for some of the inconsistencies in results from other studies. Furthermore, they suggest the possibility that NK cell function may play an important role in preventing the development of CFS in individuals who live in a community where a cluster of cases have been identified.

Copyright 2003 Wiley-Liss, Inc.

 

Source: Stewart CC, Cookfair DL, Hovey KM, Wende KE, Bell DS, Warner CL. Predictive immunophenotypes: disease-related profile in chronic fatigue syndrome. Cytometry B Clin Cytom. 2003 May;53(1):26-33. http://onlinelibrary.wiley.com/doi/10.1002/cyto.b.10034/full  (Full article)

 

Cytokines and chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) patients show evidence of immune activation, as demonstrated by increased numbers of activated T lymphocytes, including cytotoxic T cells, as well as elevated levels of circulating cytokines. Nevertheless, immune cell function of CFS patients is poor, with low natural killer cell cytotoxicity (NKCC), poor lymphocyte response to mitogens in culture, and frequent immunoglobulin deficiencies, most often IgG1 and IgG3.

Immune dysfunction in CFS, with predominance of so-called T-helper type 2 and proinflammatory cytokines, can be episodic and associated with either cause or effect of the physiological and psychological function derangement and/or activation of latent viruses or other pathogens. The interplay of these factors can account for the perpetuation of disease with remission/exacerbation cycles. A T-helper type 2 predominance has been seen among Gulf War syndrome patients and this feature may also be present in other related disorders, such as multiple chemical sensitivity. Therapeutic intervention aimed at induction of a more favorable cytokine expression pattern and immune status appears promising.

 

Source: Patarca R. Cytokines and chronic fatigue syndrome.  Ann N Y Acad Sci. 2001 Mar;933:185-200. http://www.ncbi.nlm.nih.gov/pubmed/12000020

 

alpha-Interferon treatment of patients with chronic fatigue syndrome

Abstract:

Thirty patients who fulfilled clinical criteria defined by the CDC for Chronic Fatigue Syndrome were treated with alfa 2a interferon or placebo in a double-blind crossover study. Outcome was evaluated by Natural Killer (NK) cell function, lymphocyte proliferation to mitogens and soluble antigens, CD4/CD8 counts and a 10 item Quality of Life (QOL) survey.

Although mean NK function rose from 87.8 +/- 19.6 to 129.3 +/- 20.7 lytic untis (LU; p < .05) with 12 weeks of interferon therapy, there was no significant change in the other immunologic parameters or QOL scores. When the 26 patients who completed the study were stratified according to their baseline NK function and lymphocyte proliferation, 4 groups were identified: 3 patients had normal NK cell function and lymphocyte proliferation when compared to normal, healthy controls, 9 had isolated deficiency in lymphocyte proliferation, 7 had diminished NK function only, and 7 had abnormalities for both parameters.

QOL scores were not significantly different for the four groups at baseline. After 12 weeks of interferon therapy, QOL score significantly improved in each of the seven patients with isolated NK cell dysfunction (mean score, 16.3 +/- 7.9) compared to baseline (39.7 +/- 12.1; p < .05). In these patients the mean NK function increased from 35.1 +/- 11.7 to 91.5 +/- 22.7 LU (p < .01). Significant improvement was not recorded for QOL in the other three groups. Thus, therapy with alpha interferon has a significant effect on the QOL of that subgroup of patients with CFS manifesting an isolated decrease in NK function.

 

Source: See DM, Tilles JG. alpha-Interferon treatment of patients with chronic fatigue syndrome. Immunol Invest. 1996 Jan-Mar;25(1-2):153-64. http://www.ncbi.nlm.nih.gov/pubmed/8675231

 

Immunologic abnormalities associated with chronic fatigue syndrome

Abstract:

Several aspects of cellular immunity in patients with clinically defined chronic fatigue syndrome (CFS) were evaluated and compared with those in healthy individuals.

Flow cytometric analyses revealed normal expression of total T (CD3+), B (CD19+), and NK (natural killer) (CD16+, CD56+) markers on the surface of peripheral blood mononuclear cells (PMC) from patients with CFS.

However, compared with those of healthy individuals, patients’ CD8+ T cells expressed reduced levels of CD11b and expressed the activation markers CD38 and HLA-DR at elevated levels. In many of the individuals in whom expression of CD11b was reduced the expression of CD28 was increased.

These findings indicate expansion of a population of activated CD8+ cytotoxic T lymphocytes. A marked decrease in NK cell activity was found in almost all patients with CFS, as compared with that in healthy individuals. No substantial abnormalities in monocyte activity or T cell proliferation were observed. The results of this study suggest that immune cell phenotype changes and NK cell dysfunction are common manifestations of CFS.

 

Source: Barker E, Fujimura SF, Fadem MB, Landay AL, Levy JA. Immunologic abnormalities associated with chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S136-41. http://www.ncbi.nlm.nih.gov/pubmed/8148441

 

Viral studies of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) has many characteristics suggesting persistent fatigue following a viral illness. At least nine different RNA and DNA viruses have been considered to be associated with this disease, but none of these viruses has been found to be the etiologic agent. Immunologic studies have demonstrated activated CD8+ cells and reduced function of natural killer cells suggesting a host response to an infection that has led to persistent immune disorders. Some of the symptoms of CFS may be due to cytokines produced by this hyperactive immune response to a virus that is still present in the host or that has been eliminate but leaves abnormal immunologic sequelae. These possibilities offer directions for future studies of CFS and therapeutic approaches to this condition.

 

Source: Levy JA. Viral studies of chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S117-20. http://www.ncbi.nlm.nih.gov/pubmed/8148437

 

Chronic fatigue syndrome–cases in the Kanebo Memorial Hospital

Abstract:

In our hospital, 134 patients (28 male, 106 female, 10-82 years of age) were diagnosed as having chronic fatigue syndrome (CFS). Some patients had mild elevation of antibodies against Epstein-Barr Virus and immunologic abnormalities (natural killer cell dysfunction and high rates of skin reactivity to house dust, pollen, drugs and common food). In the patients with immunologic abnormalities, we found decreases in serum concentrations of arachidonic acid and dihomogamma-linolenic acid. A Kampo medicine, Ren-Shen-Yang-Rong-Tang was used in the management of 134 patients and 98 patients returned to work or school.

 

Source: Ogawa R, Toyama S, Matsumoto H. Chronic fatigue syndrome–cases in the Kanebo Memorial Hospital. Nihon Rinsho. 1992 Nov;50(11):2648-52. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1337561

 

Chronic fatigue immune dysfunction syndrome

Abstract:

Chronic fatigue syndrome (CFS) is characterized by unexplained, debilitating fatigue or easy fatigability lasting longer than six months. While a viral basis of infection is proposed to be the cause of CFS, other viral infections do not generally persist after several weeks.

Immunological disorders, including abnormal functions and distributions of T lymphocytes, B lymphocytes, natural killer (NK) cells, and monocyte/macrophages, are described in CFS. NK cells are known to play an important role in host resistance against viral infection as well as in the regulation of the immune systems.

Restoration of NK activity resulted in recovery from CFS. Taken together, immunological abnormalities, especially dysfunction of NK cells, may be involved in CFS.

 

Source: Uchida A. Chronic fatigue immune dysfunction syndrome. Nihon Rinsho. 1992 Nov;50(11):2625-9. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1287238

 

Review of laboratory findings for patients with chronic fatigue syndrome

Abstract:

Various abnormalities revealed by laboratory studies have been reported in adults with chronic fatigue syndrome. Those most consistently reported include depressed natural killer cell function and reduced numbers of natural killer cells; low levels of circulating immune complexes; low levels of several autoantibodies, particularly antinuclear antibodies and antithyroid antibodies; altered levels of immunoglobulins; abnormalities in number and function of lymphocytes; and modestly elevated levels of two Epstein-Barr virus-related antibodies, immunoglobulin G to viral capsid antigen and to early antigen.

 

Source: Buchwald D, Komaroff AL. Review of laboratory findings for patients with chronic fatigue syndrome. Rev Infect Dis. 1991 Jan-Feb;13 Suppl 1:S12-8. http://www.ncbi.nlm.nih.gov/pubmed/1902321