Most T cells recognize antigen through the T-cell antigen receptor (TCR)alpha beta-CD3 complex on the T-cell surface. A small percentage of T cells, however, do not express alpha beta but a second type of TCR complex designated gamma delta (ref. 2). Unlike alpha beta+ lymphocytes, gamma delta+ lymphocytes do not generally express CD4 or CD8 molecules, and the nature of antigen recognition by these cells is unknown. To study antigen recognition by gamma delta+ lymphocytes we raised a gamma delta+ alpha beta- -CD4-CD8- line from an individual immune to PPD (purified protein derivative). This line showed a specific proliferative response to PPD and to a recombinant mycobacterial heat-shock protein (HSP) of relative molecular mass 65,000 (65K). The gamma delta+ line was shown to exhibit a major response to HSP in the presence of autologous antigen-presenting cells (APCs). Minor responses occurred, however, with APCs matched for some HLA class I or II antigens, whereas no response occurred with HLA-mismatched APCs. These findings, therefore, document the requirement of HSP-reactive gamma delta+ lymphocytes for histocompatible APCs.
"There is a highly probable link between innate and adaptive immune response to Mtb and a better understanding of this interaction is critical in the development of an effective vaccine. The γ/δ T cells respond rapidly to microbial epithelial invasion and are considered a component of innate immunity (Haregewoin et al., 1989; Constant et al., 1994). γ/δ T cells produce cytokines such as IFN-γ, which is important for inducing type 1 immunity. "
[Show abstract][Hide abstract] ABSTRACT: Antibiotics and vaccines are the two most successful medical countermeasures that humans have created against a number of pathogens. However a select few e.g., Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB) have evaded eradication by vaccines and therapeutic approaches. TB is a global public health problem that kills 1.4 million people per year. The past decade has seen significant progress in developing new vaccine candidates, but the most fundamental questions in understanding disease progression and protective host responses that are responsible for controlling Mtb infection still remain poorly resolved. Current TB treatment requires intense chemotherapy with several antimicrobials, while the only approved vaccine is the classical viable whole-cell based Bacille-Calmette-Guerin (BCG) that protects children from severe forms of TB, but fails to protect adults. Taken together, there is a growing need to conduct basic and applied research to develop novel vaccine strategies against TB. This review is focused on the discussion surrounding current strategies and innovations being explored to discover new protective antigens, adjuvants, and delivery systems in the hopes of creating an efficacious TB vaccine.
Frontiers in Cellular and Infection Microbiology 12/2012; 2(154):154. DOI:10.3389/fcimb.2012.00154 · 3.72 Impact Factor
"Specificity of γδ T cells to mycobacterial antigens in humans has been described . Protein antigens such as mycobacterial heat shock protein [21, 22] and nonprotein [23, 24] antigens including phosphoantigens have been shown to induce strong γδ T cell responses. In humans, the majority of studies have examined reactive patterns of the Vδ2+ subset of γδ T cells. "
[Show abstract][Hide abstract] ABSTRACT: A theme among many pathogenic mycobacterial species affecting both humans and animals is a prolonged asymptomatic or latent period that can last years to decades. The mechanisms that favor progression to active disease are not well understood. Pathogen containment is often associated with an effective cell-mediated or T-helper 1 immune profile. With certain pathogenic mycobacteria, such as Mycobacterium avium subspecies paratuberculosis, a shift to active clinical disease is associated with loss of T-helper 1 immunity and development of an ineffective humoral or T-helper 2 immune response. Recently γδ T cells have been shown to play a role early in mycobacterial infections and have been hypothesized to influence disease outcome. The purpose of this paper is to compare recent advancements in our understanding of γδ T cells in humans, cattle, and mice and to discuss roles of γδ T cells in host response to mycobacterial infection.
Veterinary Medicine International 05/2011; 2011:214384. DOI:10.4061/2011/214384
"It has been suggested that Vg9Vy2 T cells recognize bacterial HSP ( Fisch et al . , 1990 ) , but to date , only rare gy T cells have shown such reactivity ( Haregewoin et al . , 1989 ; Kabelitz et al . , 1990 ) . It is now generally assumed that Vg9Vy2 T cells preferentially recognize non - peptide anti - gens like PPP and alkylamines ( De Libero , 1997 ; Bukowski et al . , 1999 ) . The strong proliferative IPP - specific T cell responses , restricted to IOF - derived TCL with high Vg9Vy2 T cell numbers , are consis"
[Show abstract][Hide abstract] ABSTRACT: The phenotype and antigen-specificity of T cells expanded by mitogenic stimulation from intra-ocular fluid (IOF) samples of affected eyes of six Behçet's disease (BD) patients, and seven patients with other uveitis entities, were determined. High numbers of gammadelta T cells, predominantly Vgamma9Vdelta2 T cells, were only detected in the IOF-derived TCL of three BD patients. Whereas no TCL responded to heat shock protein (HSP) 65 kDa, reactivity to isopentyl pyrophosphate (IPP) and related non-peptide prenyl pyrophosphates (PPP) was restricted to the gammadelta T cell containing TCL. Upon IPP stimulation, these TCL secreted IFN-gamma but no IL-4. By single-cell analysis of intracellular IFN-gamma production and CD69 expression the IOF-derived IPP-specific T cells were identified as CD4(-)CD8(-) gammadelta T cells. The data presented suggest the infiltration of PPP-specific Vgamma9Vdelta2 Th1-like cells into the eye of BD patients with uveitis.
Journal of Neuroimmunology 10/2002; 130(1-2):46-54. · 2.47 Impact Factor
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