Generation of antigen-specific, Foxp3-expressing CD4+ regulatory T cells by inhibition of APC proteosome function.

We tested the hypothesis that immature APC, whose NF-kappaB-signaling pathway and thus maturation was blocked by the proteosome inhibitor benzyloxycarbonyl-isoleucyl-glutamyl(O-tert-butyl)-alanyl-leucinal (PSI), could be a source of Ag-specific regulatory T (Treg) cells. DO11.10 CD4(+) T cells that were incubated with Ag- and PSI-pulsed APC proliferated poorly, produced less IL-2, IFN-gamma, and IL-10 in secondary cultures, and inhibited the response of both naive and memory CD4(+) T cells stimulated by Ag-pulsed APC. The generation of PSI-APC Treg cells required IL-10 production by APC. PSI-APC Treg cell inhibition required cell-cell contact but not IL-10 or TGF-beta. Addition of IL-2 did not reverse, but Ab to CTLA-4 did reverse partially the inhibitory effect. Depletion of CD25(+) T cells before initial culture with PSI-APC did not affect Treg generation. PSI-APC Treg cells expressed high levels of Foxp3, inhibited proliferation of naive DO11.10 T cells in vivo, and abrogated colitis driven by a memory Th1 response to bacterial-associated Ag. We conclude that NF-kappaB-blocked, immature APC are able to induce the differentiation of Treg cells that can function in vitro and in vivo in an Ag-specific manner.

Management of sacrococcygeal teratoma of the fetus.

We present a case of a 22 year pregnant lady with a fetus having sacrococcygeal teratoma. The patient presented at 35 weeks of gestation with an ultrasound report showing growth at the sacral region. Emergency caesarean section was performed at 36 week and a baby girl with a huge mass on her sacral region was delivered. She was operated upon by the pediatric surgeons on the same day and the mass was excised. Histopathology of the mass confirmed the diagnosis of sacrococcygeal teratoma with an immature component. The infant is now 6 months old and there is no sign of recurrence.

Probiotics and immune regulation of inflammatory bowel diseases.

Intestinal microflora play an important role in the pathogenesis of inflammatory bowel diseases (IBD). Certain probiotic bacteria provide beneficial effects for human health and intervention of IBD. Possible mechanisms underlying these effects are diverse and include many aspects of the interaction of the host with its commensal microflora, with immunological and non-immunological effects. This review paper will focus on the recent progress in the use of probiotics in the treatment of IBD, and discuss the potential immunological mechanisms underlying their effects, such as the modulation of mucosal T cell, B cell, epithelial cell, dendrtic cell, macrophage, nature killer cell, antibody, and cytokine responses.

IFN-gamma-inducible chemokines enhance adaptive immunity and colitis.

T helper type 1 (Th1) cells secreting interferon-gamma (IFN-gamma) have been closely associated with Crohn's disease (CD). Monokine-induced by IFN-gamma (MIG), IFN-gamma-inducible T cell alpha chemoattractant (I-TAC), and IFN-gamma-inducible protein-10 (IP-10), are chemokines that bind CXCR3 and mediate the chemotaxis of leukocytes. IP-10, MIG, and CXCR3 have been shown to be expressed at sites of CD. The current study stems from our recent findings that IP-10, MIG, and I-TAC significantly contribute to the development of Th1-mediated inflammatory responses. To better understand the role of CXCR3 interactions during CD, we characterized the effects of IP-10, MIG, I-TAC, and CXCR3+ T cells on mucosal immune responses. IP-10, MIG, and I-TAC significantly enhanced antigen-specific serum and mucosal antibodies through Th1-mediated events and CD28 modulation. Additionally, the adoptive transfer of naive CXCR3+ T cells and CD4+CD45RB(HI) to T cell receptor beta (TCRbeta) x delta(-/-) mice resulted in the onset of murine colitis. Taken together, these studies suggest that IP-10, MIG, I-TAC, and CXCR3 interactions are involved in mucosal immune responses required for the induction of CD.

T helper 1 and T helper 2 cells are pathogenic in an antigen-specific model of colitis.

Dysregulated T cell responses to enteric bacteria have been implicated as a common mechanism underlying pathogenesis in rodent models of colitis. However, the bacterial species and T cell specificities that induce disease have been poorly defined. We have developed a model system in which target antigen, bacterial host, and corresponding T cell specificity are defined. OVA-specific T cells from DO11.RAG-2(-/-) TCR transgenic mice were transferred into RAG-2(-/-) recipients whose intestinal tracts were colonized with OVA-expressing or control Escherichia coli. Transfer of antigen-naive DO11.RAG-2(-/-) T cells into recipients colonized with OVA-E. coli resulted in enhanced intestinal recruitment and cell cycling of OVA-specific T cells; however, there was no development of disease. In contrast, transfer of polarized T helper (Th) 1 and Th2 populations resulted in severe wasting and colitis in recipients colonized with OVA-expressing but not control E. coli. The histopathologic features of disease induced by Th1 and Th2 transfers were distinct, but disease severity was comparable. Induction of disease by both Th1 and Th2 transfers was dependent on bacterially associated OVA. These results establish that a single bacterially associated antigen can drive the progression of colitis mediated by both Th1 and Th2 cells and provide a new model for understanding the immunoregulatory interactions between T cells responsive to gut floral antigens.