ANALYSIS OF T HELPER CELL RESPONSES DURING INFECTION WITH LEISHMANIA AMAZONENSIS (original) (raw)
Related papers
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 ...
Acta Tropica, 1994
The role played by CD4+ T lymphocytes in susceptible BALB/c mice infected with Leishmania amazonensis was investigated. Depletion ofCD4+ T cells was achieved in experimentally infected mice by means of treatment with anti-CD4 monoclonal antibody (mAb), resulting in significant reductions in the size of lesions and in mortality when compared with control animals. Moreover, th~ parasite load in the depleted mice, as quantified by limiting dilution analysis, was about 10-times lower than in the control groups. In addition, the incidence of metastases in the depleted mice was significantly reduced, and their appearance delayed as compared to the control animals. These effects correlated with a selective depletion of CD4 + T cells in the spleens of the mAb-treated mice, suggesting a role for CD4 + T cells in the aggravation of L. amazonensis infection in BALB/c mice.
European Journal of Immunology, 2002
The contribution of the costimulatory molecules B7-1 and B7-2 to the in vivo differentiation of Th cells remains controversial. The infection of resistant and susceptible strains of mice with the parasite Leishmania major provides a well-established model for studying in vivo differentiation of CD4 + T cells. We have infected B7-1/B7-2-deficient mice on the BALB/c and 129 background with L. major and subsequently examined different parameters of infection and cytokine responses upon restimulation of lymph node cells in vitro. BALB/c B7-2deficient and B7-1/B7-2-double deficient mice are resistant to L. major, whereas BALB/c B7-1-deficient mice remain as susceptible as wild-type BALB/c mice. Differential expression of B7-1 and B7-2 can explain the distinct roles observed for these B7 costimulators in L. major infection. Abbreviations: B7 dko: B7-1 -/-/B7-2 -/double knockout SLA: Soluble leishmanial antigen wt: Wild type 1764 J. A. Brown et al.
Identification of Two Distinct Subpopulations of Leishmania major-Specific T Helper 2 Cells
Infection and Immunity, 2002
It is widely accepted that a strong Th2 response is responsible for nonhealing Leishmania major infections in BALB/c mice. This Th2 response has been thoroughly documented by measuring the levels of Th2 cytokines produced by CD4 ؉ T cells present in the lymphoid organs by enzyme-linked immunosorbent assay and PCR. However, the cytokine profile of L. major-specific Th2 cells has never been determined. In this study, we used the recently described Th2 marker T1/ST2 to characterize Th2 cells during the course of nonhealing L. major infection. We analyzed the intracellular cytokine profile of CD4 ؉ T1/ST2 ؉ T cells and showed that they clearly displayed a Th2 phenotype, as they expressed interleukin 4 (IL-4), IL-10, and IL-5. In addition, we detected another population of Th2 cells among the CD4 ؉ T1/ST2 ؊ T cells that expressed IL-4 and IL-10 but excluded IL-5. In summary, we show here that two type 2 subpopulations are present in the lymphoid organs of L. major-infected BALB/c mice; Th2 cells from both subsets expressed IL-4 and IL-10, but they could be distinguished by their expression of IL-5 and T1/ST2.
Organ-specific distribution of CD4+ T1/ST2+ Th2 cells in Leishmania major infection
European Journal of Immunology, 2002
Activated CD4 + T helper cells (Th) comprise at least two functionally distinct subsets, Th1 and Th2, which mediate different immunological effector functions. Experimental leishmaniasis is widely used to study the effector function of Th cell subsets in vivo. Healing and nonhealing Leishmania major infections have been correlated with polarized Th1 and Th2 responses, respectively. In the study presented here, a stable cell surface marker expressed on Th2 cells, T1/ST2, has been used to assess the distribution of CD4 + T1/ST2 + T cells in different organs of healer and nonhealer strains of mice during the course of L. major infection. The frequency of CD4 + T cells expressing the T1/ST2 cell surface marker and Th2 cytokines in the lymphoid organs was low in both strains of infected mice; however, CD4 + T1/ST2 + T cells could be enriched from the lymphoid organs of infected nonhealer but not from healer strains of mice. The highest frequency of CD4 + T1/ST2 + T cells was detected in the footpads of mice with nonhealing disease, showing that CD4 + T1/ST2 + T cells home to the footpads. Since the majority of parasites persist at the local site of infection in nonhealing BALB/c mice, these results show that CD4 + T1/ST2 + T cells are localized at the site of active infection and inflammation in this model.
CD4+CD25+ Regulatory T Cells Restrain Pathogenic Responses during Leishmania amazonensis Infection
The Journal of Immunology, 2005
Although activation of CD4 ؉ T cells mediates pathogenesis in Leishmania amazonensis (La)-infected mice, these susceptible mice do not develop a polarized Th2 response, suggesting a unique mechanism of disease susceptibility. To understand how Th cell activities are regulated, we examined the frequency and phenotypes of regulatory T (Treg) cells. At 1-3 wk of infection, relatively high percentages of CD4 ؉ CD25 ؉ CD86 ؉ T cells, as well as high levels of FoxP3, TGF-1, and IL-10RI transcripts, were detected in the skin and draining lymph nodes, indicating local accumulation of Treg cells. Lesion-derived, IL-10-producing CD4 ؉ CD25 ؉ cells effectively suppressed proliferation and cytokine (IL-2 and IFN-␥) production of CD4 ؉ CD25 ؊ effector cells. Adoptive transfer of lesion-derived CD4 ؉ CD25 ؉ cells to syngeneic, naive C57BL/6 mice before infection significantly reduced disease development. To further validate the beneficial role of Treg cells in La infection, we adoptively transferred CD25 ؉ T cell-depleted splenocytes (derived from naive mice) into RAG1 ؊/؊ mice. This transfer rendered RAG1 ؊/؊ mice more susceptible to La infection than the mice receiving control splenocytes. The beneficial effect of Treg cells was transitory and correlated with decreased activation of IFN-␥-producing effector T cells. This study uncovers an intriguing role of Treg cells in restraining pathogenic responses during nonhealing Leishmania infection and emphasizes a balance between Treg and Th1-like effector cells in determining the outcome of New World cutaneous leishmaniasis.
Microbes and Infection, 2000
Most experimental studies on leishmaniasis compare two different inbred strains of mice that are resistant or susceptible to one species of Leishmania. In the present study we characterized some cytokines and nitric oxide production as well as histological changes related to resistance and susceptibility in isogenic CBA mice infected with Leishmania major or Leishmania amazonensis. CBA mice are capable of controlling infection with L. major, but they succumb to infection with L. amazonensis. Cells from susceptible L. amazonensis-infected CBA mice produced interleukin (IL)-4 and IL-10 but no interferon (IFN)-γ. On the other hand, resistant L. major-infected CBA mice produced IFN-γ and IL-10, but IL-4 was detected only in the first week of infection. Histopathological studies showed patterns of tissue responses at the site of the infection and in the draining lymph nodes that correlated with resistance or susceptibility. Resistant mice showed a mixed inflammatory cell infiltration and granulomas in the lesions, whereas in susceptible mice only heavily parasitized macrophages were seen. Our results indicate an important role of the parasite species in determining the pattern of immune response. L. amazonensis induces a Th2-type immune response, whereas L. major induces a Th1-type response. These factors must be identified and taken into account in the strategies for the development of vaccines against leishmaniasis. The model presented here will be useful for the study of such factors.
Western Blot Analysis of Sera from Leishmania major-Infected BALB / c and C 57 BL / 6 Mice
2013
INTRODUCTION Leishmania, a protozoan parasite, is responsible for a variety of diseases known as leishmaniasis ranging from self-healing cutaneous lesions to a fatal visceral disease. The mechanisms by which the parasite induces such a broad range of diseases are mostly unknown and involve both the pathogen and the host factors. Experimentally Leishmania (L.) major-infected mice are widely used to study the immune responses elicited against the disease. Infection with L. major in resistant C57BL/6 mice is controlled at the site of primary infection and the lesion is finally healed. Susceptible BALB/c mice, on the other hand, fail to control parasite growth and its fatal visceral spread. In these mice models, resistance and susceptibility against Leishmaina infection are determined by functionally distinct Tcell subsets. A predominant T helper 1 (Th1) response is identified by interferon-Gamma (IFNγ) and tumor necrosis factor alpha (TNFα) release. This response leads to the activatio...
Infection and Immunity, 2003
Infection of mice with Leishmania major results in disease progression or resolution, largely depending on the genetic backgrounds of the mouse strains. Infection with Leishmania amazonensis, on the other hand, causes progressive cutaneous lesions in most inbred strains of mice. We hypothesized that deficient activation of early immune responses contributes to the pathogenesis in L. amazonensis-infected mice. To distinguish early molecular events that determine the outcome of Leishmania infections, we examined cytokine gene expression in C57BL/6 mice infected with either L. amazonensis or L. major (a healing model). After 2 to 4 weeks, L.