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C Leighton

Publications and source records attributed to C Leighton.

25 records · Page 2Linked to original sources
PubMed1997

Inter-strain graft-vs.-host disease T-cell responses to immunodominant minor histocompatibility antigens.

Immunodominance affects the in vitro generation of cytotoxic T lymphocytes (CTL) specific for minor histocompatibility antigens (miHA), as exemplified in the C57BL/6By (B6) anti-BALB.B H2b-matched strain combination. Despite the potential of responding to numerous individual miHA on BALB.B antigen presenting cells, the focus of the CTL response is largely directed to only a limited number of target antigens. These miHA are differentially expressed by the CXBE, CXBG, CXBI, CXBJ, and CXBK recombinant inbred (RI) strains, all of which also express the H2b MHC haplotype. Immunodominance also plays a role in the development of lethal graft-vs.-host disease (GVHD) directed to miHA, by which B6 T cells were transplanted along with T-cell depleted bone marrow to irradiated (825 cGy) recipients of either the BALB.B or CXB RI strains. The hierarchy of immunodominance differed in GVHD from that predicted from the in vitro CTL studies; i.e., GVHD was observed in BALB.B, CXBE, CXBI, and CXBJ recipients, but not in CXBG and CXBK recipients, despite the latter two strains expressing immunodominant antigens for CTL generation. Interpretation of these results was complicated by the finding that potent GVHD could be obtained with the transfer of CXBE T cells and ATBM to irradiated CXBG recipients. To clarify the scope of the inter-strain immunodominant interactions involved in GVHD in these strain combinations and to estimate the minimum number of miHA that could be responsible for GVHD, a full panel of GVHD responses was analyzed. The GVHD potential was evaluated for donor T cells derived from both parental RI strains as well as for (B6 x RI)F1 hybrids to restrict responses to only those miHA originating from BALB.B origin. The results were consistent with the minimal involvement of two distinct immunodominant miHA in the B6-->BALB.B lethal GVHD response. One immunodominant miHA (GVH-1) appeared to be shared by the CXBE, CXBI, and CXBJ RI strains, while the second antigen (GVH-2) was uniquely expressed by the parental BALB.B strain.

Animals↗
PubMed1997

Peptide analogs that inhibit IgE-Fc epsilon RI alpha interactions ameliorate the development of lethal graft-versus-host disease.

Significant increases in serum levels of IgE have often been observed in allogeneic bone marrow transplantation patients and have generally been thought to be diagnostic of graft-versus-host disease (GVHD), rather than an agent involved in the pathogenesis of the disease. Experimental murine GVHD models have also indicated associations of hyper-IgE activity, yet the role of IgE in GVHD pathogenesis has never been tested directly. In the current study, we have tried to address this issue by using recently developed peptide analog antagonists for the interaction of IgE with the Fc epsilon RI receptor, which is necessary for triggering mast cells and other cell types when cross-linked by antigens. A synthetic cyclized 13-amino acid peptide was previously designed from the modeled C-C' loop region of the Fc epsilon RI alpha-chain and was found to act as a competitive inhibitor of IgE-Fc epsilon RI alpha binding. The peptide was generated in two forms, a cyclic L-(L-IgEtide) and retro D-amino acid composition (rDIgEtide), the latter to increase resistance to protease degradation for in vivo applications. These two inhibitor peptides were then used to test the hypothesis that IgE could be involved in the pathogenesis of acute GVHD, in the B10.D2-->DBA/2 (900 cGy) strain combination, with GVHD directed to minor histocompatibility antigens. Both peptides demonstrated significant inhibition of the development of lethal GVHD, supporting the involvement of IgE at some level of disease pathogenesis.

Animals↗
PubMed1995

Protecting the poor under cost recovery: the role of means testing.

In African health sectors, the importance of protecting the very poor has been underscored by increased reliance on user fees to help finance services. This paper presents a conceptual framework for understanding the role means testing can play in promoting equity under health care cost recovery. Means testing is placed in the broader context of targeting and contrasted with other mechanisms. Criteria for evaluating outcomes are established and used to analyze previous means testing experience in Africa. A survey of experience finds a general pattern of informal, low-accuracy, low-cost means testing in Africa. Detailed household data from a recent cost recovery experiment in Niger, West Africa, provides an unusual opportunity to observe outcomes of a characteristically informal means testing system. Findings from Niger suggest that achieving both the revenue raising and equity potential of cost recovery in sub-Saharan Africa will require finding ways to improve informal means testing processes.

Africa↗
PubMed1994

Graft-versus-myeloid leukemia responses following syngeneic and allogeneic bone marrow transplantation.

A model for investigating graft-versus-leukemia (GVL) activity following syngeneic and MHC-compatible allogeneic BMT has been developed in C57BL/6 (B6) mice with use of the c-myc retrovirus-transformed MMB3.19 myeloid leukemia line. The MMB3.19 line was derived from a B6 mouse and expresses monocyte/macrophage markers, including Mac-1, Mac-2, F4/80, and LFA-1, in addition to H-2 class I and class II molecules. A challenge dosage of 10(5) of these leukemia cells was found to be completely lethal when injected into irradiated (850 cGy) B6 recipients, 1 day after the transplantation of syngeneic donor T cell-depleted-bone marrow. The addition of T lymphocytes to the donor inoculum prolonged recipient survival, and both CD4+ and CD8+ subsets were found to be capable of mediating this GVL activity. For the MHC-compatible allogeneic model, the C3H.SW-->B6 (850 cGy) strain combination was utilized, in which CD8+ T cells are known to cause graft-versus-host disease directed to minor histocompatibility antigens expressed by the recipient. In this case, both CD(4+)- and CD(8+)-enriched T cells were found to be capable of mediating GVL activity to MMB3.19 challenge, particularly if donor mice were presensitized with leukemia cells. Of most significance, only the donor CD4+ T cells mediated a GVL effect without the apparent induction of graft-versus-host disease.

Animals↗