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A human islet transplant can cure patients with type 1 diabetes. A drawback of islet transplantation is the life-long immunosuppressive medication, often associated with severe side effects. Moreover, in spite of the immunosuppressive therapy, islets are lost in the majority of transplanted patients over time. An improved small animal model for studies on human islet allograft rejection mechanisms and the development of new measures for its prevention is clearly warranted. Here, we evaluated the potential of Balb/cRag2−/−γc−/− mice carrying a human-like immune system (so-called humanized mice) as a tool for studies on the rejection of transplanted human islets. Human T cells from Balb/cRag2−/−γc−/− mice, which as neonates had been transplanted with CD34+ human cord blood haematopoietic stem cells (HIS mice), proliferated in response to allogeneic human dendritic cells, but failed to reject a human islet allograft transplanted to the renal subcapsular space as assessed by immunohistochemistry and analysis of human serum C-peptide levels. Histological analysis revealed that few if any T cells had migrated to the grafted tissue. These observations question the usefulness of the HIS mouse model for studies on human islet allograft rejection mechanisms and highlight the need for further improvements. [ABSTRACT FROM AUTHOR]

Chlamydia pneumoniae initiates infection in humans via the mucosal epithelia of the respiratory tract; therefore, immunity at this mucosal site is believed to be important to control infection with this pathogen. We compared the protective capacity of immunization in mice with two C. pneumoniae antigens, namely the major outer membrane protein (MOMP) and the heat shock protein 60 (HSP-60), against intranasal (i.n.) infection with the bacteria when given as protein or DNA and when administered by i.n. or intraperitoneal (i.p.) routes. Our data showed that i.n. immunizations with both antigens delivered as DNA were protective against C. pneumoniae infection, probably due to induction of cell-mediated immune responses. Our study also revealed that i.n. immunizations with MOMP, but not with HSP-60, given as protein induced protective local immune responses in the respiratory tract against C. pneumoniae infection. Moreover, no protection was induced by either antigen when the i.p. route of immunization was used. We further investigated in immunoglobulin (Ig)A-deficient mice whether the reduction in the bacterial loads observed when MOMP was administered intranasally was related to the strong local IgA responses induced by this route of immunization. Our data showed that IgA-deficient mice were more susceptible to infection than wild-type mice, suggesting that the induction of local IgA responses may play a role in the protection of the respiratory tract against C. pneumoniae infections. [ABSTRACT FROM AUTHOR]

We have studied the expression of IFN-γ, IL-2 and IL-2 receptor (IL-2R) at the mRNA and protein levels in spleen and lymph node cells from Trypanosoma cruzi-infected BALB/c mice. At 21 days post infection (dpi) (peak of parasitaemia), spleen cells stimulated with Con A for 16 h showed a reduced IFN-γ, IL-2 and IL-2R mRNA production compared with non-infected controls. Lymph node cells obtained at 4, 21 or 60 dpi produced similar amounts of IFN-γ, IL-2 or IL-2R transcripts after mitogen stimulation as uninfected controls. Spleen cells obtained at 21 dpi showed a lower Con A proliferative response and IL-2R expression compared with non-infected controls, while the proliferation and IL-2R expression of lymph node cells at 21 dpi was unaltered. Supernatants from 48 h Con A-stimulated spleen and lymph node cells from mice at 21 dpi had very low levels of IL-2 but contained significantly higher levels of IFN-γ compared with the supernatants of cells from non-infected mice. The latter phenomenon correlates with an accelerated rate of IFN-γ mRNA accumulation. [ABSTRACT FROM AUTHOR]

The role of CD4+ T lymphocytes in the resistance of BALB/c mice to Trypanosoma cruzi was examined by in vivo depletion using monoclonal anti-CD4 antibodies (MoAbs). When the administration of MoAbs was initiated 2 days before, or 5 to 12 days after the infection (dpi) with 50 bloodstream-form trypomastigotes of the Tulahuén strain, mice showed an enhanced susceptibility lo the parasite. Specific IgG, but not IgM responses, were inhibited in anti-CD4- treated and infected mice. However, when anti-CD4 treatment of mice was delayed until the 8th week of infection, neither a reactivation of the infection as determined by mortality or parasitaemia, nor a modulation of the titre of anti-T. cruzi IgG antibodies was detected. Furthermore, mice chronically infected with T. cruzi and deprived of CD4+ T cells resisted the challenge with 50,000 trypomastigotes (approximately 1000 LD50). Secondary antibody responses against parasite antigens were inhibited after in vitro depletion of CD4+ cells in chronically infected mice before boosting with T. cruzi antigens. However, recipients of CD4 or T-cell-depleted spleen cells from mice chronically infected with T. cruzi were protected when challenged with the parasite. The possibility that the parasite control is maintained by long-lived B cells capable of rapid differentiation into IgG-secreting plasma cells in the absence of T helper cells is discussed considering the present data. [ABSTRACT FROM AUTHOR]

A massive activation of T cells lakes place during the early stages of a Trypanosoma cruzi infection in mice. We present data indicating that substantial amounts of interleukin 2 (IL-2) are secreted and IL-2 receptors are expressed during the period of increased proliferation (4-7 days post Infection), Both concanavalin A-induced proliferation and IL-2 production are markedly decreased later in the acute infection (around 3 weeks post infection). This proliferation cannot be restored by externally added IL-2. Simultaneously, there is a drastic reduction in the number of both high- and low-affinity IL-2 receptors. The reduction is not attributable to the elimination of a particular T-cell population. In vivo administration of recombinant IL-2 failed to improve resistance to T. cruzi parasites as measured by parasitaemia and mortality. [ABSTRACT FROM AUTHOR]

T lymphocytes provide a major line of defence against many protozoan parasites. The aim of this work was to determine the role of T-cell helper/inducer subset (T h/i) in the resistance to Trypanosoma cruzi in a routine model. The importance of natural killer (NK) cells in the resistance to the parasite was also evaluated. BALB/c and C57BL/6 mice were injected with or with a polyclonal rabbit either monoclonal antibodies against L3T4, Thy 1.2, NK1.1, antiserum against NK cells (anti-asialo GM-1). The effect of in vivo administration of these antibodies was tested in separate functional assays. After antibody treatment, mice were infected with a low dose of T. cruzi in the bloodstream form. Mice depleted of, or reduced in T, T h/i, or NK cell activity all developed higher parasitacmia and had higher mortality than their control counterparts. Mice injected with anti-L3T4 monoclonal antibodies were unable to generate a specific antibody response to the parasite. Treatment of mice with alpha/beta interferon, which is known to boost N K cell activity, resulted in an enhanced resistance to the parasite. Our data indicate that T h/i cells as well as NK cells, are of vital importance in controlling parasitaemia and reducing mortality in T. cruzi-infected mice. Finally, we also demonstrate that the production of antibodies specific for T. cruzi is strictly T helper cell-dependent. [ABSTRACT FROM AUTHOR]