Role of CD4+ T cells in pathogenesis associated with Leishmania amazonensis infection (original) (raw)
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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.
Infection and Immunity, 2004
A T-cell clone (designated KLmB-3) was derived from resistant C3H mice 2 weeks after infection with Leishmania major. KLmB-3 was a CD4-T-cell clone that utilized the Vβ8.1 T-cell receptor. When adoptively transferred to naive C3H mice, KLmB-3 unexpectedly exacerbated infection with L. major (it increased the cutaneous lesion size and the parasite burden within the lesion). The ability of KLmB-3 to exacerbate disease correlated with its ability to produce the type 2-associated cytokines interleukin-4 (IL-4), IL-5, IL-10, and transforming growth factor beta. Interestingly, KLmB-3 was specific for an epitope in the amino-terminal end of the L. major surface gp63 zinc metalloproteinase (leishmanolysin) that has been shown to be capable of inducing a protective immune response. Moreover, KLmB-3 was activated when this epitope was presented in the context of H-2 I-E rather than H-2 I-A.
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.
ANALYSIS OF T HELPER CELL RESPONSES DURING INFECTION WITH LEISHMANIA AMAZONENSIS
2002
Most inbred strains of mice are susceptible to Leishmania amazonensis infection and develop progressive cutaneous lesions. However, the role of Th subsets in the disease and the molecular basis of pathogenesis are unclear. To address this issue, we examined the frequency of cytokine-producing CD4+ T cells and the profile of T cell receptor (TCR) usage in infected BALB/c mice. At
International Immunology
Although CD4 + T cells are generally accepted to be responsible for the determination of resistance to infection in experimental murlne cutaneous lelshmanlasls, a contribution of CD8 + lymphocytes to Immunity can be demonstrated under certain well-defined conditions. Normally highly susceptible BALB/c mice can be rendered resistant to Infection with Leishmania major promastigotes by a single Injection of monoclonal anti-CD4 antibodies at the beginning of Infection. Mice treated In such a way can heal their primary cutaneous lesions and acquire immunity to subsequent challenge Infection. Both the resolution of the primary Infection and the Induced state of Immunity to reinfection In these mice Is shown to be dependent upon the antilelshmanlal effector functions of CD8+ T cells. Furthermore, In contrast to control Infected BALB/c mice, which are unable to mount a delayed-type hypersensltivity (DTH) response to viable parasites, mice cured as a result of treatment with antl-CD4 antibodies In vivo exhibit a strong DTH response, which can be significantly reduced by Injection of either antl-CD4 or antl-CD8 monoclonal antibodies prior to antigenlc challenge with viable promastigotes. Moreover, Increased numbers of specific CD8 + T cells, able to transfer Le/shman/a-speclflc DTH responses, were found In lymphold organs of BALB/c mice rendered resistant to Infection by Immunolnterventlon with anti-CD4 monoclonal antibodies at the beginning of infection. Neutralization In vivo of Interleukln 4 during the course of infection In BALB/c mice also enables these otherwise susceptible mice to resolve their cutaneous lesions and to decrease the parasite burden In Infected tissues. CD8+ T cells are required for both of these beneficial effects. Taken together, these results indicate that In the immune BALB/c mouse, as in the normally resistant CBA mouse, CD8 + lymphocytes are Involved In the elimination of L. major and in the establishment and maintenance of Immunity against infection with this parasite.
European Journal of Immunology, 2012
Primary Leishmania major infection typically produces cutaneous lesions that heal but that harbor persistent parasites. While the opposing roles of CD4 + T cell-derived IFN-γ and IL-10 in promoting parasite killing and persistence have been well established, how these responses develop from naïve precursors has not been directly monitored throughout the course of infection. We used peptide:Major Histocompatibility Complex II (pMHCII) tetramers to investigate the endogenous, parasite-specific primary CD4 + T cell response to L. major in mice resistant to infection. Maximal frequencies of IFN-γ + CD4 + T cells were observed in the spleen and infected ears within a month after infection and were maintained into the chronic phase. In contrast, peak frequencies of IL-10 + CD4 + T cells emerged within 2 weeks of infection, persisted into the chronic phase, and accumulated in the infected ears but not the spleen, via a process that depended on local antigen presentation. T helper type-1 (Th1) cells, not Foxp3 + regulatory T cells, were the chief producers of IL-10 and were not exhausted. Therefore, tracking antigen-specific CD4 + T cells revealed that IL-10 production by Th1 cells is not due to persistent T cell antigen receptor stimulation, but rather driven by early antigen encounter at the site of infection.