Cd4+ T cell response to leishmania spp. in non-infected individuals (original) (raw)
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Clinical and Experimental Immunology, 2004
SUMMARY Regulation of the immune response directed against Leishmania is critical for the establishment of effective control of the disease. It is likely that some types of immune responses directed against Leishmania can lead to more severe clinical forms of leishmaniasis causing a poor control of the pathogen and/or pathology, while others lead to resolution of the infection with little pathology as in cutaneous leishmaniasis. To gain a better understanding of the possible role that subpopulations of T cells, and their associated cytokines have on disease progression and/or protective immune responses to L. braziliensis infection, a detailed study of the frequency of activated and memory T cells, as well as antigen specific, cytokine producing T cells was carried out. Following the determination of cytokine producing mononuclear cell populations in response to total Leishmania antigen (SLA), and to the recombinant antigen LACK, correlation analysis were performed between specific ...
Role of CD4+ T cells in pathogenesis associated with Leishmania amazonensis infection
Journal of immunology (Baltimore, Md. : 1950), 1997
Most inbred strains of mice are susceptible to Leishmania amazonensis infection. We have examined the mechanism(s) underlying this generalized susceptibility using mice deficient in T cell development or in the expression of either MHC class I or class II. In contrast to wild-type C57BL/6 (B6) mice that uniformly developed large ulcerating lesions, mice lacking functional CD4+ T cells (due to targeted disruption of genes for either MHC class II trans-activator or I-A beta) showed no signs of lesion development for up to 12 to 14 wk postinfection and contained significantly lower numbers of parasites in lesions. Similarly, both B6 nude and RAG2 -/- mice failed to develop lesions. However, RAG2 -/- mice reconstituted with naive wild-type CD4+ T cells and beta2m -/- mice did develop lesions. Lesions of MHC class II -/- mice contained minimal numbers of CD8+ T cells, a marked reduction of monocytes/macrophages, and evident extracellular parasites. The inability to mount an inflammatory ...
Profile of human T cell response to leishmanial antigens. Analysis by immunoblotting
Journal of Clinical Investigation, 1989
Control and resolution of leishmanial infection depends primarily on T cell-mediated immune mechanisms. The nature of the leishmanial antigens involved in eliciting T cell immunity is unknown. We have examined the pattern of peripheral blood lymphocyte responses in patients with active, healed, or subclinical leishanial infection to fractionated leishmanial antigens using a T cell immunoblotting method in which nitrocellulose-bound leishmanial antigens, resolved by one or two dimensional electrophoresis, are incorporated into lymphocyte cultures. The proliferative and IFN-'y responses of cells from patients with healed mucosal or cutaneous leishmaniasis were remarkably heterogeneous and occurred to as many as 50-70 distinct antigens. In contrast, responses from subjects with active, nonhealing, diffuse cutaneous leishmaniasis were either absent or present to only a small number of antigens. Control and resolution of leish is, and resistance to reinfection, is therefore associated with a T cell response to a large and diverse pool of parasite antigens. The method of T cell immunoblotting appears to offer a powerful, rapid, and relatively simple approach to the identification of antigens involved in eliciting a T cell response in human leishmaniasis. Address reprint requests to Dr. David Sacks, Building 5, Room 112,
European Journal of Immunology, 1989
Immunity to experimental infection with Leishmania major: generation of protective L3T4' T cell clones recognizing antigen(s) associated with live parasites* Exacerbation and resolution of lesions induced by Leishmania major promastigotes are, at least in part, the result of the activity of distinct parasite-specific L3T4' T lymphocytes. The present report describes L. major-specific cloned L3T4+ T lymphocytes capable of transferring substantial protective immunity to normal highly susceptible BALB/c mice. The two protective T cell clones analyzed appear to recognize antigen associated only with live L. major parasites. Therefore, the pattern of antigen reactivity of these protective T cell clones is different from that of the previously described parasite-specific L3T4' T cells which contribute to exacerbation of disease. The results presented in this report indicate that the two opposite effects of parasitespecific L3T4' T cells on the disease process could be mediated by functionally similar L3T4' T cells differing in their antigen specificity.
Cell biology and immunology of Leishmania
Immunological Reviews, 2011
More than 20 years ago, immunologists discovered that resistance and susceptibility to experimental infection with the intracellular protozoan Leishmania major was associated with the development of T-helper 1 (Th1)-and Th2-dominated immune responses, respectively. This infectious disease model was later used to identify and assess the role of key factors, such as interleukin-12 (IL-12) and IL-4, in Th1 and Th2 maturation. While infection by Leishmania remains a popular model for immunologists who wish to assess the role of their favorite molecule in T-cell differentiation, other investigators have tried to better understand how Leishmania interact with its insect and mammalian hosts. In this review, we discuss some of these new data with an emphasis on the early events that shape the immune response to Leishmania and on the immune evasion mechanisms that allow this parasite to avoid the development of sterilizing immunity and to secure its transmission to a new host.
International Immunopharmacology, 2008
Cellular immune responses directed against protozoan parasites are key for controlling pathogen replication and disease resolution. However, an uncontrolled, or improperly controlled, response can be deleterious to the host in terms of both allowing for the establishment of pathology, as well as less effective establishment of memory responses. Human cutaneous leishmaniasis is a disease caused by the infection with Leishmania spp. following a bite from the sandfly, the natural vector of this disease. Tens of millions worldwide are currently infected with Leishmania and no effective vaccines have been developed to date. In the face of the complexity presented by the interaction between a host (humans) with the parasite, Leishmania, and the fact that this parasite is inoculated by another complex, biologically active, vector, the sandfly, it is clearly important to study the immunoregulatory mechanisms that are induced in humans naturally infected by this parasite if we hope to develop effective vaccines and immunotherapeutic treatments in the future. Our laboratory has focused over the years on the study of the local and systemic T cell response during the first episode of cutaneous leishmaniasis suffered by individuals before they undergo antimony treatment. The goal of this review is to briefly outline our findings with hopes of putting our most recent studies concerning the dichotomy between alpha/beta TCR and gamma/delta TCR expressing, CD4-CD8-(double negative-DN) T cells in the context of a balanced immune response against Leishmania and to discuss the implications of these findings toward our understanding of human leishmaniasis.
Clinical and Experimental Immunology, 1994
The T ceil response to antigens from Lei.shtnania major promastigoles was investigated in peripheral biood mononuclear cells from Sudanese individuals with a history of cutaneous leishmaniasis (CL), Sudanese individuals with positive DTH reaction in the leishmanin skin test but wilh no history of skin lesions, and in Danes without known exposure to Leishmania parasites. Proliferation and production of interferon-gamma (IF''N-7) and IL-4 in aniigen-stimulaied eultures was measured. Lymphocytes from individuals with a history of CL proliferated vigorously and produced IFN-7 afler stimulation with either a crude preparation of L. major antigens or the major surface protease gp63. These cullures produced no or onty little IL-4. Also celis from leishmanin skin test-positive donors wilh no history of CL produced IFN-7 and no lL-4 in response to /,. major antigens. Cells from the unexposed Danes were nol activated by gp63. The cells from Danish donors produced either IFN-7 or IL-4, but not bolh cytokines after incubation with the crude preparation of L. major antigens. The dala show that the T cell response to Leishmania antigens in humans who have had uncomplicated CL or subelinical L. major infection is an IFN-7-producing Thl-like response.
Infection and Immunity, 1989
Immunity in human leishmaniasis is mediated by sensitized T lymphocytes; however, the antigens involved in eliciting this immunity have not been defined. We describe the generation of human T-lymphocyte clones derived from two patients with healed leishmaniasis. By use of one- and two-dimensional cellular immunoblotting techniques, we directly identified the parasite antigens recognized by these clones. To our knowledge, these are the first leishmanial antigens identified to which CD4+, gamma interferon-producing T cells from immune individuals have been shown to respond, the strategy may be of general use for the identification of antigens involved in immunity in this disease.
2013
Resolution of leishmanial infection is dependent on the coordinated interactions between components of cell mediated immune response, central to which is the activation of targeted T-cell populations for appropriate cytokine production and activation of infected cells. In human as well as murine leishmaniasis, cure is associated with predominant Th1 response, good cell-mediated immunity (CMI), production of interferon gamma (IFN-γ) and macrophage activation. On the other hand, cytokine analysis in visceral leishmaniasis reveals enhanced induction of IL-10 and⁄or IL-4 mRNA in tissues, poor CMI, hypergammaglobulinaemia and enhanced presence of IL-4 in circulation of patients with progressive disease. The Th1/Th2 paradigm of resistance/susceptibility is an oversimplication of a far more complicated network of regulatory/counterregulatory interactions and thus a deficit in the understanding of the exact mechanisms involved in resolution vs severity of leishmaniasis. This review, in addition to giving a general overview of basic immunology of Leishmania infection, consolidates findings on immune responses in experimental and human leishmaniasis. Such information is important in giving a feasible direction in designing prophylactic and therapeutic strategies against leishmaniasis.
Mediators of Inflammation, 2014
The nature of effector cells and the potential immunogenicity of Leishmania major excreted/secreted proteins (LmES) were evaluated using peripheral blood mononuclear cells (PBMCs) from healed zoonotic cutaneous leishmaniasis individuals (HZCL) and healthy controls (HC). First, we found that PBMCs from HZCL individuals proliferate and produce high levels of IFN-and granzyme B (GrB), used as a marker of activated cytotoxic T cells, in response to the parasite antigens. IFN-is produced by CD4 + T cells, but unexpectedly GrB is also produced by CD4 + T cells in response to stimulation with LmES, which were found to be as effective as soluble Leishmania antigens to induce proliferation and cytokine production by PBMCs from immune individuals. To address the question of regulatory T cell (Tregs) involvement, the frequency of circulating Tregs was assessed and found to be higher in HZCL individuals compared to that of HC. Furthermore, both CD4 + CD25 + and CD4 + CD25 − T cells, purified from HZCL individuals, produced IFN-and GrB when stimulated with LmES. Additional experiments showed that CD4 + CD25 + CD127 dim/− Tregs were involved in GrB production. Collectively, our data indicate that LmES are immunogenic in humans and emphasize the involvement of CD4 + T cells including activated and regulatory T cells in the immune response against parasite antigens.