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Microbial Antigens (microbial + antigen)
Selected AbstractsMicrobial colonization induces oligoclonal expansions of intraepithelial CD8 T cells in the gutEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2004Lars Helgeland Abstract Two populations of CD8+ IEL generally express restricted, but apparently random and non-overlapping TCR repertoires. Previous studies in mice suggested that this could be explained by a dual origin of CD8+ IEL, i.e. that CD8,,+ IEL derive from a few peripheral CD8+ T cell lymphoblasts stimulated by microbial antigens in gut-associated lymphoid tissue, whereas CD8,,+ IEL descend from an inefficient intestinal maturation pathway. We show here that the gut mucosa, instead, becomes seeded with surprisingly broad and generally non-overlapping CD8 IEL repertoires and that oligoclonality is induced locally after microbial colonization. In germ-free (GF) rats, both CD8,,+ and CD8,,+ IEL displayed surprisingly diverse TCR V, repertoires, although ,-chain diversity tended to be somewhat restricted in the CD8,,+ subset. CDR3 length displays in individual V,-C, and V,-J, combinations generally revealed polyclonal distributions over 6,11 different lengths, similar to CD8+ lymph node T cells, and CDR3, sequencing provided further documentation of repertoire diversity. By contrast, in ex-GF rats colonized with normal commensal microflora, both CD8,,+ and CD8,,+ IEL displayed oligoclonal CDR3 length distributions for most of the V, genes analyzed. Our data suggest that microbial colonization induces apparently random clonal expansions of CD8,,+ and CD8,,+ IEL locally in the gut. [source] Rapid and reliable generation of invariant natural killer T-cell lines in vitroIMMUNOLOGY, Issue 3 2009Asako Chiba Summary Several tools have proved useful in the study of invariant natural killer T (iNKT) cells, including CD1d-deficient mice, J,281-deficient mice, synthetic lipid antigens and antigen-loaded CD1d tetramers. However, the generation and examination of long-term primary murine iNKT cell lines in vitro has been challenging. Here, we show the rapid generation of iNKT cell lines from splenic iNKT cells of V,14 T-cell receptor (TCR) transgenic (Tg) mice. These purified iNKT cells were stimulated by bone marrow-derived dendritic cells (BMDCs) loaded with ,-galactosylceramide (,GalCer) and cultured with interleukin (IL)-2 and IL-7. iNKT cells proliferated dramatically, and the cell number exhibited a 100-fold increase within 2 weeks and a 105 -fold increase in 8 weeks after repeated stimulation with ,GalCer. The iNKT cell lines consisted of iNKT cells expressing V, chains including V,8.1/8.2, V,14, V,10, V,6 and V,7, and responded to stimulation with ,GalCer presented both by BMDCs and by plate-bound CD1d. In addition, the iNKT cell lines produced interferon (IFN)-, when activated by lipopolysaccharide (LPS) or CpG oligodeoxynucleotide (ODN)-stimulated BMDCs. Further, we show that iNKT cell lines produced cytokines in response to microbial antigens. In summary, high-yield iNKT cell lines were generated very rapidly and robustly expanded, and these iNKT cells responded to both TCR and cytokine stimulation in vitro. Given the desire to study primary iNKT cells for many purposes, these iNKT cell lines should provide an important tool for the study of iNKT cell subsets, antigen and TCR specificity, activation, inactivation and effector functions. [source] ,, T-cell anergy in human immunodeficiency virus-infected persons with opportunistic infections and recovery after highly active antiretroviral therapyIMMUNOLOGY, Issue 4 2000F. Martini Summary ,, T lymphocytes recognize non-peptidic microbial antigens without antigen processing and major histocompatibility complex (MHC) restriction, representing an early defence mechanism against invading pathogens. As a defective response to non-peptidic antigens was observed in human immunodeficiency virus-positive (HIV+) persons, the aims of this study were twofold: to analyse the incidence of ,, T-cell anergy in HIV+ patients with opportunistic infections/co-infections (HIV-OIC), and to investigate the role of highly active antiretroviral therapy (HAART) on ,, T-cell functions. Peripheral ,, T-cell distribution and in vitro reactivity to a non-peptidic mycobacterial antigen, isopentenyl pyrophosphate (IPP), were analysed. ,, T-cell subset distribution was altered more in HIV-OIC patients than in asymptomatic HIV+ subjects (HIV-ASY). Specifically, the V,2/V,1 ratio was inverted as a consequence of a decrease in V,2 T-cell number. Moreover, IPP-stimulated V,2 T cells from the HIV-OIC group displayed a major defect in interferon-, (IFN-,) production. Interestingly, HAART induced a sustained recovery of naive CD45RA+ and CD62L+ T cells and restored ,, T-cell function. Accordingly, in vitro CD45RA depletion resulted in ,, T-cell hyporesponsiveness. Altogether, the incidence of ,, T-cell anergy was increased in HIV-OIC patients and dependent on CD45RA helper function. Moreover, HAART was able to restore ,, T-cell reactivity, extending the immune recovery to non-peptidic microbial antigens. [source] Scientific rationale for the Finnish Allergy Programme 2008,2018: emphasis on prevention and endorsing toleranceALLERGY, Issue 5 2009L. C. Von Hertzen ,In similarity to many other western countries, the burden of allergic diseases in Finland is high. Studies worldwide have shown that an environment rich in microbes in early life reduces the subsequent risk of developing allergic diseases. Along with urbanization, such exposure has dramatically reduced, both in terms of diversity and quantity. Continuous stimulation of the immune system by environmental saprophytes via the skin, respiratory tract and gut appears to be necessary for activation of the regulatory network including regulatory T-cells and dendritic cells. ,Substantial evidence now shows that the balance between allergy and tolerance is dependent on regulatory T-cells. Tolerance induced by allergen-specific regulatory T-cells appears to be the normal immunological response to allergens in non atopic healthy individuals. Healthy subjects have an intact functional allergen-specific regulatory T-cell response, which in allergic subjects is impaired. Evidence on this exists with respect to atopic dermatitis, contact dermatitis, allergic rhinitis and asthma. Restoration of impaired allergen-specific regulatory T-cell response and tolerance induction has furthermore been demonstrated during allergen-specific subcutaneous and sublingual immunotherapy and is crucial for good therapeutic outcome. However, tolerance can also be strengthened unspecifically by simple means, e.g. by consuming farm milk and spending time in nature. ,Results so far obtained from animal models indicate that it is possible to restore tolerance by administering the allergen in certain circumstances both locally and systemically. It has become increasingly clear that continuous exposure to microbial antigens as well as allergens in foodstuffs and the environment is decisive, and excessive antigen avoidance can be harmful and weaken or even prevent the development of regulatory mechanisms. ,Success in the Finnish Asthma Programme was an encouraging example of how it is possible to reduce both the costs and morbidity of asthma. The time, in the wake of the Asthma Programme, is now opportune for a national allergy programme, particularly as in the past few years, fundamentally more essential data on tolerance and its mechanisms have been published. In this review, the scientific rationale for the Finnish Allergy Programme 2008,2018 is outlined. The focus is on tolerance and how to endorse tolerance at the population level. [source] The increasing prevalence of allergy: a challenge for the physicianCLINICAL & EXPERIMENTAL ALLERGY REVIEWS, Issue 1 2002R. Mösges Summary The prevalence of allergic disorders has increased markedly throughout the world during the past three decades. There has been considerable controversy about the extent to which the increase is real, or attributable to increased awareness or better diagnosis. It seems probable that the increased prevalence is real because longitudinal studies have shown a rapid exponential increase in allergic disorders such as asthma. Since there is a marked difference in the occurrence of allergic disorders between Western and less developed countries, as well as between rural and urban areas, it is likely that environmental (,lifestyle') factors are aetiologically involved. It also seems probable that contact with microbial antigens, in the form of childhood infections, vaccinations and contact with farm animals, can exert some protection against the later development of allergies. Studies are in progress to determine whether reduction in risk factors or intervention with anti-allergic therapies can modify the long-term outcome in populations at high risk. [source] | ||||||||||||||||||||||