ABSTRACT
We have investigated the effects of dietary nucleotides on intraepithelial lymphocytes (IEL) and intestinal epithelial cells (IEC) in weanling mice. The proportion of T-cell receptor (TCR) gammadelta+ IEL in BALB/c mice fed a diet supplemented with nucleotides (NT(+) diet) was significantly higher than that in mice fed the nucleotide-free diet, while the proportion of TCR alphabeta+ IEL in NT(+) diet-fed mice was significantly decreased. The change of the TCR alphabeta+/TCR gammadelta+ ratio was mainly observed in a CD8 alphaalpha+ subset of IEL. IEC from NT(+) diet-fed mice produced a higher level of IL-7, which is important in the development of TCR gammadelta+ IEL, than those from control diet-fed mice. The expression levels of IL-7 and IL-2 receptors on IEL were not different between the two dietary groups. Our findings suggest that the increased population of a TCR gammadelta+ IEL subset by feeding nucleotides may be caused by the increased production of IL-7 by IEC.
Subject(s)
Cytidine Monophosphate/metabolism , Dietary Supplements , Guanosine Monophosphate/metabolism , Inosine Monophosphate/metabolism , Interleukin-7/biosynthesis , Receptors, Antigen, T-Cell, gamma-delta/metabolism , T-Lymphocyte Subsets/metabolism , Uridine Monophosphate/metabolism , Animals , Epithelial Cells/metabolism , Female , Humans , Intestinal Mucosa/cytology , Intestinal Mucosa/metabolism , Lymphocyte Count , Mice , Mice, Inbred BALB C , Receptors, Interleukin-2/biosynthesis , Receptors, Interleukin-7/biosynthesis , T-Lymphocyte Subsets/classification , T-Lymphocyte Subsets/cytologyABSTRACT
BACKGROUND: Oral immunotherapy with a peptide for allergic immune responses is theoretically a promising therapy but has not been established yet. OBJECTIVE: To evaluate immune suppressive efficacy of oral administration of an immunodominant peptide, we investigated changes in T-cell proliferation, TH1 - and TH2 -cytokine production, and TH1 - and TH2 -mediated antibody production in mice after oral administration of a peptide. METHODS: Peptide p246-259, containing a dominant T-cell determinant of Cry j 2, which is the major allergen in Japanese cedar pollen, was used in this study. Groups of mice received p246-259 or PBS alone before or after they were primed intranasally with Cry j 2 and cholera toxin. In another experiment mice were primed intraperitoneally with Cry j 2 and alum. Proliferative response and cytokine production by nasal-associated lymph node cells against Cry j 2 were investigated. Amounts of systemic anti-Cry j 2 IgE and IgG antibodies were also measured. RESULTS: Oral administration of the peptide to mice before, or even after, the sensitization induced oral tolerance in T-cell responses against the allergen; the tolerance was associated with decreased production of TH1 (IFN-gamma and IL-2) and TH2 (IL-4) cytokines. Allergen-specific TH1 -mediated (IgG2a and IgG2b) and TH2 -mediated (IgG1 and IgE) antibody responses were also inhibited. CONCLUSIONS: Oral administration of a dominant T-cell determinant peptide induces immunologic tolerance in both TH1 and TH2 cell responses against the whole protein allergen. Our study is the first, to our knowledge, to demonstrate the potential for peptide-based oral immunotherapy in order to treat allergic immune responses.
Subject(s)
Allergens/administration & dosage , Epitopes, T-Lymphocyte/administration & dosage , Immunodominant Epitopes/administration & dosage , Peptides/immunology , Plant Proteins/administration & dosage , Th1 Cells/immunology , Th2 Cells/immunology , Administration, Intranasal , Administration, Oral , Animals , Cells, Cultured , Cholera Toxin/immunology , Female , Immune Tolerance/drug effects , Immune Tolerance/immunology , Immunoglobulin E/biosynthesis , Immunoglobulin G/biosynthesis , Lymph Nodes/cytology , Lymph Nodes/drug effects , Lymph Nodes/immunology , Lymphocyte Activation , Mice , Mice, Inbred BALB C , Nasal Mucosa/cytology , Nasal Mucosa/immunology , Peptides/administration & dosage , Pollen/immunology , TreesABSTRACT
A subset of type 2, but not type 1, CD4 T cell clones expresses IL-3R and can be stimulated by IL-3. Expression of IL-3R on these type 2 T cell clones is induced by TCR stimulation, and subsequent stimulation by IL-3 augmented the proliferation of and IL-4 production by these cells. This augmented response is inhibited by anti-IL-4 mAb, suggesting the involvement of IL-4 in this response. In place of TCR stimulation, treatment of these type 2 CD4 T cell clones with PMA rendered them responsive to further stimulation of proliferation by IL-3, indicating the cooperation between the IL-3R-elicited signals and PKC-mediated signals in stimulating proliferation. Although the augmentation of the TCR-mediated proliferative response by IL-3 was mainly due to the increased production of IL-4, we also demonstrated the presence of IL-4-independent mechanism mediating the response to IL-3. In situ, we found that splenic T cells could be induced to respond to Il-3 by TCR stimulation. Thus, IL-3 can stimulate a specific population of T cells and influence the immune response.