Through study of cutaneous basophil hypersensitivity (CBH) it is now clear that basophils and mast cells, their contained mediators (such as histamine and serotonin), and their associated anaphylactic antibodies (IgE and IgG1), are involved in delayed-time course reactions. These findings mean that immune components improtant in allergic disease and astha are also potentially important in immune resistance to microbes and parasites and in rejection of tumors and tissue grafts. This research proposal submits a comprehensive program for the continued investigation of the role of antibodies in CBH responses of guinea pigs. We will study the mechanism by which these antibodies mediate CBH by determining whether circulating basophils, and basophils arriving at CBH reactions are sensitized with antibodies that transfer CBH. We will also determine whether these antibodies are a special subclass of IgG1 and whether lymphocytes or macrophages are involved in the ability of antibodies to mediate CBH. Finally, studies will be performed to determine whether these antibodies are also involved in CBH reactions that are transferred by thymic-derived lymphocytes (T cells). Studies will also be continued on the requirement for T cells to activate mast cells to release the vasoactive amine serotonin in murine delayed-type hypersensitivity (DTH). Serotonin transport from mast cells in DTH, and in vitro will be studied. A mast cell-derived serotonin protein that may be important in transport of serotonin will be characterized. Finally, we will determine the mechanism by which T cells may activate mast cells in DTH by determining whether non-specific serotonin releasing lymphokines, or specific IgF-like factors are involved.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI012211-21
Application #
2059865
Study Section
Special Emphasis Panel (NSS)
Project Start
1977-06-01
Project End
1997-05-31
Budget Start
1994-06-01
Budget End
1995-05-31
Support Year
21
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Yale University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Kalish, R S; Askenase, P W (1999) Molecular mechanisms of CD8+ T cell-mediated delayed hypersensitivity: implications for allergies, asthma, and autoimmunity. J Allergy Clin Immunol 103:192-9
Szczepanik, M; Ptak, W; Askenase, P W (1999) Role of interleukin-4 in down-regulation of contact sensitivity by gammadelta T cells from tolerized T-cell receptor alpha-/- mice. Immunology 98:63-70
Szczepanik, M; Lewis, J; Geba, G P et al. (1998) Positive regulatory gamma delta T cells in contact sensitivity: augmented responses by in vivo treatment with anti-gamma delta monoclonal antibody, or anti-V gamma 5 or V delta 4. Immunol Invest 27:1-15
Ushio, H; Tsuji, R F; Szczepanik, M et al. (1998) IL-12 reverses established antigen-specific tolerance of contact sensitivity by affecting costimulatory molecules B7-1 (CD80) and B7-2 (CD86). J Immunol 160:2080-8
Ptak, W; Paliwal, V; Bryniarski, K et al. (1998) Aggregated immunoglobulin protects immune T cells from suppression: dependence on isotype, Fc portion, and macrophage FcgammaR. Scand J Immunol 47:136-45
Szczepanik, M; Nowak, B; Askenase, P W et al. (1998) Cross-talk between gammadelta T lymphocytes and immune cells in humoral response. Immunology 95:612-7
Szczepanik, M; Anderson, L R; Ushio, H et al. (1997) Gamma/delta T cells from tolerized alpha/beta-TCR-deficient mice antigen specifically inhibit contact sensitivity in vivo and IFN-gamma production in vitro. Int Arch Allergy Immunol 113:373-5
Matsuda, H; Ushio, H; Geba, G P et al. (1997) Human platelets can initiate T cell-dependent contact sensitivity through local serotonin release mediated by IgE antibodies. J Immunol 158:2891-7
Geba, G P; Wegner, C D; Wolyniec, W W et al. (1997) Nonatopic asthma: in vivo airway hyperreactivity adoptively transferred to naive mice by THY-1(+) and B220(+) antigen-specific cells that lack surface expression of CD3. J Clin Invest 100:629-38
Tsuji, R F; Geba, G P; Wang, Y et al. (1997) Required early complement activation in contact sensitivity with generation of local C5-dependent chemotactic activity, and late T cell interferon gamma: a possible initiating role of B cells. J Exp Med 186:1015-26

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