Innate immunity in asthma

Asthma is a complex and heterogeneous disease with several phenotypes. Most studies have focused on allergic asthma associated with allergen sensitization and adaptive immunity. On the other hand, nonallergic asthma is associated with a number of environmental factors such as infection, air pollution, or obesity, and requires innate immunity rather than adaptive immunity. In the lung, a number of innate immune cells and mechanisms have evolved to lead lung inflammation and asthma. These innate mechanisms include innate cytokines and various innate cells, including innate lymphoid cells, natural killer cells, as well as gammadelta T cells, which together produce a wide range of cytokines, independent of adaptive immunity and conventional antigens. Here, we review the most recent works regarding innate immune cells and the mechanisms underlying their role in asthma.

Comparative Analysis of Human Epidermal and Peripheral Blood gammadelta T Cell Cytokine Profiles

BACKGROUND: Human epidermal gammadelta T cells are known to play crucial roles in the defense and homeostasis of the skin. However, their precise mechanism of action in skin inflammation remains less clear. OBJECTIVE: In this study, we analyzed the cytokine expression profile of human epidermal gammadelta T cells and compared it to that of peripheral blood gammadelta T cells to investigate the specific activity of epidermal gammadelta T cells in modulating skin inflammation. METHODS: We isolated gammadelta T cells from epidermal tissue or peripheral blood obtained from healthy volunteers. Isolated gammadelta T cells were stimulated using immobilized anti-CD3 antibody and interleukin-2 plus phytohaemagglutinin, and were then analyzed using a cytokine array kit. RESULTS: Both epidermal and peripheral blood gammadelta T cells produced comparable levels of granulocyte-macrophage colony-stimulating factor, I-309, interferon-gamma, macrophage migration inhibitory factor, macrophage inflammatory protein-1alpha, and chemokine (C-C) ligand 5. The epidermal gammadelta T cells produced significantly higher levels of interleukin-4, -8, -13, and macrophage inflammatory protein-1beta than the peripheral blood gammadelta T cells did. Notably, the epidermal gammadelta T cells produced several hundred-fold higher levels of interleukin-13 than interleukin-4. CONCLUSION: These results suggest that the epidermal gammadelta T cells have a stronger potential to participate in the Th2-type response than the peripheral blood gammadelta T cells do. Furthermore, epidermal gammadelta T cells might play an important role in the pathogenesis of Th2-dominant skin diseases because of their active production of interleukin-13.

γδ T cells response to Mycobacterium tuberculosis in pulmonary tuberculosis patients using preponderant complementary determinant region 3 sequence.

Background & objectives: The unique immunological functions of γδ T lymphocytes to contribute immunity against Mycobacterium tuberculosis attracted interest of researchers. However, little is known about the specificity of γδ Τ cell in tuberculosis patients and the lack of exact tuberculosis antigen recognized by γδ T cells limited its application. The analysis of complementary determinant region (CDR)3 sequence characteristic in γδ T cells of tuberculosis patients would contribute to understand the distribution specificity of γδ T cell. In present study, we investigated the diversity of the γ9/δ2 T cell immunorepertoire and analysed the specificity of the expressed CDR3 in pulmonary tuberculosis patients. Methods: The total RNA in peripheral blood mononuclear cell of 50 pulmonary tuberculosis patients and 10 healthy controls was extracted. The polymerase chain reaction was used to specifically amplify the CDR3 region of γ9 and δ2 chain. The PCR products were ligated into the pGEM-T easy vector. The plasmid DNA was sequenced using the ABI3700 and the T7 primer. Results: Our findings showed that predominant CDR3 sequence of δ2 chain in pulmonary tuberculosis patients was CACDTLVSTDKLIFGKG. The sequence specifically exists in almost all pulmonary tuberculosis patients. The conserved hydrophobic acid residue in 97 positions is present in the γδ T cell reactive to M. tuberculosis. The length of δ2 CDR3 in pulmonary tuberculosis patients has no relation with the disease progress. Interpretation & conclusions: Our results suggest that γδ T cells appear to use CDR3 sequence to recognise M. tuberculosis antigen. γδ T cells reactive to M. tuberculosis were diverse and polyclonal.

Phenotypic and functional analysis of bovine gammadelta lymphocytes

The studies have provided the first comprehensive comparison of the factors regulating activation and proliferation of WC1+ and WC1- gammadelta T cells. The investigation has shown that accessory molecules essential for activation and function of WC1+ and WC1- gammadelta T cells and the sources and roles of cytokines in activation of gammadelta T cells through the T cell receptor (TCR). The study has also shown that the role of cytokines in activation and function of gammadelta T cells activated indirectly through cytokines secreted by ab T cells, accessory cells and antigen presenting cells (APC). Cytokines were differentially produced by subpopulations of gammadelta T cells under different conditions of activation. The investigation obtained in this study has revealed that factors account for activation and proliferation of gammadelta T cells in cultures designed to study MHC-restricted responses to antigens. Evidence obtained here has shown there is biological relevance to activation under these culture conditions that points to potential regulatory and effector functions of gammadelta T cells. The investigations have also provided the information needed to begin identifying and characterizing antigens recognized by the TCR repertoires of WC1+ and WC1- gammadelta T cells. Finally, the investigations have provided the information needed to begin analysis of the mechanisms by which gammadelta T cells modulate MHC restricted immune responses to pathogens and derived vaccines.