T Cell Zones of Lymphoid Organs Constitutively Express Th1 Cytokine mRNA: Specific Changes during the Early Phase of an Immune Response

ABSTRACTHantaan virus (HTNV) infection can cause a severe lethal hemorrhagic fever with renal syndrome (HFRS) in humans. CD8+T cells play a critical role in combating HTNV infections. However, the contributions of different CD8+T cell subsets to the immune response against viral infection are poorly understood. Here, we identified a novel subset of CD8+T cells characterized by the CD8lowCD100−phenotype in HFRS patients. The CD8lowCD100−subset accounted for a median of 14.3% of the total CD8+T cells in early phase of HFRS, and this percentage subsequently declined in the late phase of infection, whereas this subset was absent in healthy controls. Furthermore, the CD8lowCD100−cells were associated with high activation and expressed high levels of cytolytic effector molecules and exhibited a distinct expression profile of effector CD8+T cells (CCR7+/−CD45RA−CD127highCD27intCD28lowCD62L−). When stimulated with specific HTNV nucleocapsid protein-derived peptide pools, most responding CD8+cells (gamma interferon [IFN-γ] positive and/or tumor necrosis factor alpha [TNF-α] positive) were CD8lowCD100−cells. The frequency of CD8lowCD100−cells among HTNV-specific CD8+T cells was higher in milder cases than in more severe cases. Importantly, the proportion of the CD8lowCD100−subset among CD8+T cells in early phase of HFRS was negatively correlated with the HTNV viral load, suggesting that CD8lowCD100−cells may be associated with viral clearance. The contraction of the CD8lowCD100−subset in late phase of infection may be related to the consistently high expression levels of PD-1. These results may provide new insights into our understanding of CD8+T cell-mediated protective immunity as well as immune homeostasis after HTNV infection in humans.IMPORTANCECD8+T cells play important roles in the antiviral immune response. We found that the proportion of CD8lowCD100−cells among CD8+T cells from HFRS patients was negatively correlated with the HTNV viral load, and the frequency of CD8lowCD100−cells among virus-specific CD8+T cells was higher in milder HFRS cases than in more severe cases. These results imply a beneficial role for the CD8lowCD100−cell subset in viral control during human HTNV infection.

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Interrelationship of feeding with immunity and parasitic infection: a review

Veterinární Medicína ◽

10.17221/2028-vetmed ◽

2008 ◽

Vol 52 (No. 4) ◽

pp. 131-143 ◽

Cited By ~ 15

Author(s):

S.Gy. Fekete ◽

R.O. Kellems

Keyword(s):

Immune Response ◽

T Cell ◽

Hypersensitivity Reaction ◽

Feed Intake ◽

Parasitic Infection ◽

Lymphoid Organs ◽

The Body ◽

Strong Positive Correlation ◽

Phase Reaction ◽

Voluntary Feed Intake

Authors overlook the recent findings in the field of the complex interrelationship among nutrition, immune status and parasitic infestation. After summarizing the general characteristics of the active immune system, they describe the first period of the systemic immune response, the acute phase reaction. The cause of drastical decrease in serum zinc concentration is redistribution into the liver and lymphocyte metallothioneins. Immune deficiency correlates only indirectly with the nutrition. Ingestion of feed mycotoxins (e.g. T-2 toxin) and peroxides causes lymphocytes depletion in the lymphoid organs. Events of immunological stress are a special form of homeorrhetic control. Lack of energy and protein hardly damages the humoral immunity. Undernutrition fundamentally affects the cell-mediated immune response and the complement production. In animals, the lack of calcium, magnesium, iron, zinc, copper, iodine and selenium has been associated with signs of immunodeficiency. The concentrations of trace elements required for healthy animals are often below what is required for animals experiencing an immunological challenge. Zinc has both specific and aspecific role in the immune defence mechanism. Zinc regulates the maturation and function of immune cells, among others by protecting developing lymphocytes from apoptosis. As part of the zinc-finger proteins, may influence DNA transcription. The thymus synthesizes a 9-amino acid peptide hormone, the thymulin, which is activated after having bound zinc. Selenium has a vitamin E-independent immunostimulant effect in the marginally supplied animals. Active form of vitamin D<sub>3</sub> regulates transcription at cell level, acts as an immunomodulator and promotes phagocytosis. Lack of essential fatty acids in the diet of experimental animals caused atrophy of lymphoid organs and the reduction both the T-cell mediated and the independent immune response. Practical application of the new immunological findings is the segregated early weaning (SEW). Feed allergy results either in immediate hypersensitivity reaction within 1 to 2 hours or a T cell-mediated delayed hypersensitivity reaction within days. Under a certain number of worms (“threshold value”) the host organism did not show detectable changes. Parasitic infection changes the body and skeletal composition: the water content increases, that of protein and fat drop; the calcium and phosphorus concentration of bones decreases. Helminths, developing in the animal, may cause serious local lesions; anaemia and the change of plasma proteins. Worms’ toxins stimulate the production of gastrointestinal hormones, causing reduction in voluntary feed intake. Rabbits with biliary coccidiosis significantly decreased voluntary feed intake and the digestibility of the fats. The extent of infection and the oocyte excretion of <i>Eimeria maxima</i> in growing chickens showed a strong negative correlation with the plasma carotenoid level and strong positive correlation with the blood nitrogen oxide and γ-interferon concentration.

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“Galectin-1 Induces Central and Peripheral Cell Death: Implications in T-Cell Physiopathology”

Developmental Immunology ◽

10.1155/2000/36321 ◽

2000 ◽

Vol 7 (2-4) ◽

pp. 117-129 ◽

Cited By ~ 13

Author(s):

C. E. Sotomayor ◽

G. A. Rabinovich

Keyword(s):

Immune Response ◽

Immune System ◽

T Cell ◽

Therapeutic Potential ◽

Inflammatory Diseases ◽

Lymphoid Organs ◽

Peripheral Cell ◽

Contact Exposure ◽

Induced Apoptosis ◽

Complex Scenario

The immune system has a remarkable capacity to maintain a state of equilibrium even as it responds to a diverse array of foreign proteins and despite its contact exposure to self-antigens. Apoptosis is one of the mechanisms aimed at preserving the homeostasis after the completion of an immune response, thus returning the immune system to a basal state and warranting the elimination of autoagressive cells in both central and peripheral lymphoid organs. Targeted deletions in critical genes involved in the apoptotic death machinery together with natural spontaneous mutations have clearly shown the importance of apoptosis in the regulation of the immune response. This complex scenario of stimulatory and inhibitory genes has been enriched with the finding that galectin-1, a 14.5 kDa β-galactoside-binding protein, is able to induce apoptosis of immature cortical thymocytes and mature T cells by cross-linking cell surface glycoconjugates. Galectin-1 is present not only in central and peripheral lymphoid organs, but also at sites of immune privilege. In the present article we will discuss the implications of galectin-1-induced apoptosis in T-cell physiopathology in an attempt to validate its therapeutic potential in autoimmune and inflammatory diseases.

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Anatomical and Cellular Requirements for the Activation and Migration of Virus-Specific CD8+ T Cells to the Brain during Theiler's Virus Infection

Journal of Virology ◽

10.1128/jvi.79.5.3063-3070.2005 ◽

2005 ◽

Vol 79 (5) ◽

pp. 3063-3070 ◽

Cited By ~ 16

Author(s):

Yanice V. Mendez-Fernandez ◽

Michael J. Hansen ◽

Moses Rodriguez ◽

Larry R. Pease

Keyword(s):

Bone Marrow ◽

Immune Response ◽

T Cells ◽

T Cell ◽

Cell Response ◽

T Cell Response ◽

Lymphoid Organs ◽

Antigen Presenting Cell ◽

Antigen Presenting ◽

The Brain

ABSTRACT Theiler's murine encephalomyelitis virus (TMEV) infection of the brain induces a virus-specific CD8+ T-cell response in genetically resistant mice. The peak of the immune response to the virus occurs 7 days after infection, with an immunodominant CD8+ T-cell response against a VP2-derived capsid peptide in the context of the Db molecule. The process of activation of antigen-specific T cells that migrate to the brain in the TMEV model has not been defined. The site of antigenic challenge in the TMEV model is directly into the brain parenchyma, a site that is considered immune privileged. We investigated the hypothesis that antiviral CD8+ T-cell responses are initiated in situ upon intracranial inoculation with TMEV. To determine whether a brain parenchymal antigen-presenting cell is responsible for the activation of virus-specific CD8+ T cells, we evaluated the CD8+ T-cell response to the VP2 peptide in bone marrow chimeras and mutant mice lacking peripheral lymphoid organs. The generation of the anti-TMEV CD8+ T-cell response in the brain requires priming by a bone marrow-derived antigen-presenting cell and the presence of peripheral lymphoid organs. Although our results show that activation of TMEV-specific CD8+ T cells occurs in the peripheral lymphoid compartment, they do not exclude the possibility that the immune response to TMEV is initiated by a brain-resident, bone marrow-derived, antigen-presenting cell.

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Hematopoietic stem cells engineered to release cytokines: A way of targeting lymphoid organs to modulate immune response?

Immunology Letters ◽

10.1016/s0165-2478(97)86994-5 ◽

1997 ◽

Vol 56 (1-3) ◽

pp. 41

Author(s):

N Wettschureck

Keyword(s):

Stem Cells ◽

Immune Response ◽

Hematopoietic Stem Cells ◽

Lymphoid Organs ◽

Hematopoietic Stem

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How Far we are towards Eradication of HBV Infection

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld.2014.1121.244.hbv ◽

2015 ◽

Vol 24 (4) ◽

pp. 473-479 ◽

Cited By ~ 4

Author(s):

Mihai Voiculescu

Keyword(s):

Immune Response ◽

Hepatitis B Virus ◽

T Cell ◽

Hepatitis B ◽

T Cell Receptors ◽

Hepatitis B Surface Antigen ◽

Hbv Infection ◽

Major Health Problem ◽

Cell Receptors ◽

B Virus

Hepatitis B virus (HBV) infection is a major health problem with an important biological and a significant socio-economic impact all over the world. There is a high pressure to come up with a new and more efficient strategy against HBV infection, especially after the recent success of HCV treatment. Preventing HBV infection through vaccine is currently the most efficient way to decrease HBV-related cirrhosis and liver cancer incidence, as well as the best way to suppress the HBV reservoir. The vaccine is safe and efficient in 80-95% of cases. One of its most important roles is to reduce materno-fetal transmission, by giving the first dose of vaccine in the first 24 hours after birth. Transmission of HBV infection early in life is still frequent, especially in countries with high endemicity.Successful HBV clearance by the host is immune-mediated, with a complex combined innate and adaptive cellular and humoral immune response. Different factors, such as the quantity and the sequence of HBV epitope during processing by dendritic cells and presenting by different HLA molecules or the polymorphism of T cell receptors (TOL) are part of a complex network which influences the final response. A new potential therapeutic strategy is to restore T-cell antiviral function and to improve innate and adaptive immune response by immunotherapeutic manipulation.It appears that HBV eradication is far from being completed in the next decades, and a new strategy against HBV infection must be considered. Abbreviations: ALT: alanine aminotransferase; APC: antigen presenting cells; cccDNA: covalently closed circular DNA; HBIG: hepatitis B immunoglobulin; HbsAg: hepatitis B surface antigen; HBV: hepatitis B virus; HCC: hepatocellular carcinoma; CTL: cytotoxic T lymphocyte; IFN: interferon; NUC: nucleos(t)ide analogues; pg RNA: pre genomic RNA; TLR: toll-like receptors; TOL: T cell receptors.

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