The long term objective of this project is to regulate antigen uptake by M cells and transport to lymphoid cells in intestinal lymphoid organs. The ability to target M cells with probes adherent to M cells will be investigated in mouse and rabbit animal models. Transport of a mouse monoclonal antibody against the rabbit M cell surface will be compared to a monoclonal antibody that does not bind to M cell surfaces. Since these mouse monoclonal antibodies are also foreign proteins to rabbits, levels of antigen specific IgA in mucosal secretions will be studied to determine whether binding will enhance generation of a mucosal immune response. Lectins which bind to M cells will be used as vectors to enhance antigen uptake by M cells and development of a subsequent IgA immune response. The ability to regulate uptake of particles by M cells will be examined in vivo by using fluorescent microspheres of two different colors conjugated to M cell binding lectins. M cells which have been stimulated by gamma- interferon to express cell surface la will be targeted with anti-la:antigen conjugates. The effect of antigen uptake by M cells on the activation of mucosal T cells will be defined. Activation of T cells will be determined by detection of a T cell activation molecule on mucosal T cells and rabbit T cell lines. The ability of M cells to convey activation signals in vivo will be examined after mitogen binding to M cell surfaces. The capacity of activated T cells to selectively bind to M cells will be assessed in vitro to determine factors involved in infiltration of M cells by lymphocytes. Understanding M cell uptake of antigens and particles is relevant for optimizing oral immunization, combating intestinal infection, and delineating the pathogenesis of mucosal immunologic diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK038550-06
Application #
3237949
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1992-07-15
Project End
1996-06-30
Budget Start
1992-07-15
Budget End
1993-06-30
Support Year
6
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Acambis, Inc.
Department
Type
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Kabok, Z; Ermak, T H; Pappo, J (1995) Microdissected domes from gut-associated lymphoid tissues: a model of M cell transepithelial transport in vitro. Adv Exp Med Biol 371A:235-8
Ermak, T H; Bhagat, H R; Pappo, J (1994) Lymphocyte compartments in antigen-sampling regions of rabbit mucosal lymphoid organs. Am J Trop Med Hyg 50:14-28
Sakaguchi, S; Ermak, T H; Toda, M et al. (1994) Induction of autoimmune disease in mice by germline alteration of the T cell receptor gene expression. J Immunol 152:1471-84
Ohtsuka, A; Piazza, A J; Ermak, T H et al. (1992) Correlation of extracellular matrix components with the cytoarchitecture of mouse Peyer's patches. Cell Tissue Res 269:403-10
Owen, R L; Piazza, A J; Ermak, T H (1991) Ultrastructural and cytoarchitectural features of lymphoreticular organs in the colon and rectum of adult BALB/c mice. Am J Anat 190:10-8
Shellito, J; Suzara, V V; Blumenfeld, W et al. (1990) A new model of Pneumocystis carinii infection in mice selectively depleted of helper T lymphocytes. J Clin Invest 85:1686-93
Carteron, N L; Wofsy, D; Schimenti, C et al. (1990) F(ab')2 anti-CD4 and intact anti-CD4 monoclonal antibodies inhibit the accumulation of CD4+ T cells, CD8+ T cells, and B cells in the kidneys of lupus-prone NZB/NZW mice. Clin Immunol Immunopathol 56:373-83
Ermak, T H; Steger, H J; Pappo, J (1990) Phenotypically distinct subpopulations of T cells in domes and M-cell pockets of rabbit gut-associated lymphoid tissues. Immunology 71:530-7
Owen, R L; Ermak, T H (1990) Structural specializations for antigen uptake and processing in the digestive tract. Springer Semin Immunopathol 12:139-52
Ermak, T H; Steger, H J; Pappo, J (1990) Intrathymic changes in murine CD3, CD5 and CD8 expression after in vivo administration of anti-CD4. Immunobiology 180:351-61

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