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Biomedical subjects

J Sypek

Publications and source records attributed to J Sypek.

5 recordsLinked to original sources
PubMed1997

Characterization of T cell-mediated responses in nonhealing and healing Leishmania major infections in the absence of endogenous IL-4.

IL-4 drives polarized Th2 responses, and differentiating Th2 cells down-regulate their sensitivity to IL-12. Therefore, the failure of BALB/c mice to heal Leishmania major infection could be due to an IL-4-dependent biased Th2 response or to a reduced capacity of Leishmania-specific Th cells to respond to IL-12. We examined the ability of CD4+ Th cells from L. major-infected wild-type and IL-4-deficient BALB/c mice to respond to IL-12. We show that the inability of normal and IL-4-deficient BALB/c mice to heal L. major infections is due to their inability to generate effective Th1 responses and not to persistent IL-4-dominated Th2 responses. Redirection of immune responses in vivo by administration of IL-12 or anti-CD4 mAb treatment in the early phase of infection (+/-12 days) allows both normal and IL-4-deficient BALB/c mice to heal their lesions by allowing them to develop an efficient Th1 response regardless of the presence or the absence of IL-4. Finally, on a population level, Ag-specific Th cells from infected animals induced to heal display a strongly elevated response to IL-12.

Adjuvants, Immunologic↗
PubMed1996

Interleukin-12 and -10 and gamma interferon regulate polyclonal and ligand-specific expansion of murine B-1 cells.

B-1 cells (CD5+ B220+) are a self-replenishing lineage of B cells which are autoreactive and capable of producing large amounts of interleukin-10 (IL-10). In mice experimentally infected with the human helminth parasite Schistosoma mansoni, expansion of B-1 cells is seen in the peritoneal cavity just prior to egg laying. In naive mice, B-1 cell expansion can be elicited by intraperitoneal injection of saline soluble egg antigens (SEA) or the polylactosamine sugar lacto-N-fucopentaose III (LNFPIII), which contains the Lewis-X trisaccharide. In this study, we demonstrate that LNFPIII is the major stimulus in SEA responsible for expansion of B-1 cells, since SEA-induced B-1 outgrowth is blocked by multiple injections of non-cross-linked free LNFPIII. IL-10 is an autocrine growth factor for B-1 cells, and we show that B-1 outgrowth after SEA and LNFPIII administration is inhibited by injection of anti-IL-10 antibodies. Furthermore, SEA- and LNFPIII-induced expansion of B-1 cells is inhibited by in vivo administration of recombinant murine IL-12 or recombinant gamma interferon. These data suggest that activation and expansion of IL-10-producing B-1 cells are governed via cross-regulatory cytokines.

Animals↗
PubMed1995

IL-12 increases resistance of BALB/c mice to Mycobacterium tuberculosis infection.

IL-12, a cytokine produced by macrophages and B cells, has recently been found to exert pleiotropic effects on the immune system. When BALB/c mice, a strain highly susceptible to virulent Mycobacterium tuberculosis infection, were given IL-12 at the initiation of infection with M. tuberculosis, their mean survival time doubled from 58 to 112 days. IL-12-treated mice had diminished bacterial burdens, whereas treatment with exogenous IFN-gamma had no effect on survival or bacterial burden. IL-12 treatment also delayed lung pathology in BALB/c mice. In contrast with the findings in the BALB/c model, IL-12 did not increase survival of M. tuberculosis-infected gko mice, transgenic mice in which the IFN-gamma gene has been disrupted, indicating that IL-12 does not induce protection against tuberculosis in mice in the absence of IFN-gamma.

Animals↗
PubMed1994

Interleukin 12: a key modulator of immune function.

Interleukin (IL)-12 was cloned on the basis of its ability to activate natural killer (NK) cells and promote the development of cytolytic T cells. With further understanding of its activities, IL-12 has emerged as an important cytokine, affecting both immune and hematologic functions. It has been shown to be necessary for the T cell independent induction of interferon (IFN)-gamma, critical for the initial suppression of bacterial and parasitic infection; for the development of a Th1 response, critical for effective host defense against intracellular pathogens; and for the activation of differentiated T lymphocytes of both CD4+ and CD8+ phenotype. IL-12 thus functions to activate and to link the innate and acquired immune responses. The therapeutic potential of these activities is suggested by studies in tumor and microbial models. IL-12 has suppressed tumor growth in all murine models examined. Antimicrobial activity has been demonstrated in bacterial, yeast, parasitic, and viral models of infection. In many of these models, activity has been linked to production of IFN-gamma and, in the parasite model, to development of a Th1 response. In addition to the therapeutic potential associated with IL-12 activity in these disease models, the understanding of its role in immune development and interaction with other cytokines, particularly antagonists, such as IL-4 and IL-10, has clarified and extended our understanding of immune regulation and should lead to significant developments in understanding the progression of AIDS and the development of vaccine adjuvants able to direct the immune response.

Animals↗