The Journal of immunology : official journal of the American Association of Immunologists
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Differentiation of naive CD4+ lymphocytes into either Th1 or Th2 cells is influenced by the cytokine present during initial Ag priming. IL-4 is the critical element in the induction of Th2 response; however, its origin during a primary immune response is not well defined. In the present study, we characterized a novel potential source of IL-4, the class I-selected CD4-CD8-TCR-alpha beta+ T cells. ⋯ Peripheral CD4-CD8-TCR-alpha beta+ T cells express high levels of IL-4 mRNA in response to in vivo anti-CD3 challenge. Furthermore, analysis performed in mice lacking MHC class I or class II molecules demonstrates that both the class I-selected subset of CD4-CD8-TCR+ and CD4+ peripheral T lymphocytes are the major IL-4 producers after in vivo anti-CD3 stimulation. These findings suggest that class I-selected CD4-CD8-TCR-alpha beta+ and CD4+ T cell populations are important sources of IL-4 probably implicated in the development of specific Th2 immune responses.
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Lymphocyte-specific protein 1 (LSP1) was originally reported as a lymphocyte-specific actin-binding protein using murine LSP1 probes. Subsequently, we identified LSP1 in polymorphonuclear neutrophils (PMN) and showed that it is the overexpressed 47-kDa protein in neutrophil actin dysfunction with 47- and 89-kDa abnormalities. This suggests that regulation of LSP1 expression in myeloid cells may be a functionally important event. ⋯ The results show that LSP1 is expressed in all human leukocytes, and its expression is up-regulated during granulocytic and monocytic differentiation of myeloid cells in vitro. Since its overexpression is implicated in the functional pathogenesis of a novel human neutrophil motile dysfunction and microfilamentous cytoskeletal abnormality (NAD 47/89), finding LSP1 in all human leukocytes suggests that it plays a role in regulating microfilamentous cytoskeleton structure and motile function in all leukocytes. Since the protein is not lymphocyte specific and is an F-actin binding protein, and its isoforms are expressed in stromal and embryonic mesenchymal cells, we propose that the protein's name be changed to leufactin, as an abbreviated form of leukocyte F-actin binding protein.
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Studies have shown that graft-vs-host disease (GVHD) in animal models induces persistent elevated levels of circulating adrenal glucocorticoids. In this report, we investigated the effects of endogenous glucocorticoids on the outcome of GVHD by adrenalectomizing (ADX) unirradiated (C57BL/6 x A)F1 (B6AF1) mice before GVHD induction. GVHD was induced by injection of 20 x 10(6) A strain parental lymphoid cells into B6AF1 mice. ⋯ The marked reduction of parental cells and recovery from GVHD were prevented by treating ADX F1 mice with either exogenous glucocorticoid, anti-asialoGM1, or anti-CD8, but not anti-NK1.1 Ab. These results suggest that a dramatic recovery from GVHD was induced by a cell-mediated, steroid-sensitive F1-anti-parental mechanism. The F1-anti-parental phenomenon described herein is different from classical hybrid resistance.
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The role of macrophage inflammatory protein-1 alpha (MIP-1 alpha) in the pathogenesis of acute lung injury in rats after intrapulmonary deposition of IgG immune complexes or intratracheal administration of LPS has been assessed. Critical to these studies was the cloning and functional expression of rat MIP-1 alpha. The resulting product shared 92% and 90% homology with the known murine sequence at the cDNA level and protein level, respectively. ⋯ Under such conditions, in both models TNF-alpha content in BAL fluids was substantially reduced as compared with BAL fluids from positive control animals. These findings suggest that rat MIP-1 alpha plays an important role in the development of lung injury in these neutrophil-dependent models. The role of MIP-1 alpha seems to be related to production of TNF-alpha, which in turn up-regulates vascular adhesion molecules required for neutrophil influx.
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Comparative Study
Structure and repertoire usage of rat TCR alpha-chain genes in T cells infiltrating heart allografts.
We have studied the structure and diversity of TCR alpha-chain genes used by graft-infiltrating lymphocytes (GIL) in the ACI-to-LEW rat cardiac allograft model. We previously reported the structure of 16 different V alpha and 17 different J alpha genes isolated in two different cDNA libraries established from LEW thymocytes and GIL. In this report, we obtained new sequence information for 17 additional V alpha and J alpha genes from the GIL cDNA library. ⋯ As for the TCR alpha-chain repertoire usage in allograft rejection, we completed the characterization of 36 productively rearranged TCR alpha-chain cDNA clones from the GIL cDNA library and found 31 different V alpha and 23 different J alpha genes among these clones. Unlike the TCR beta-chain that uses a limited repertoire, the alpha-chain repertoire usage seems to be relatively more diverse in this allograft model. These results suggest that the interaction of beta-chain with allogeneic MHC-encoded determinants may dictate the T cell reaction to the heart allograft in this model.