Effect of in Vivo Depletion of CD4+ and CD8+ Cells on the Induction and Maintenance of Oral Tolerance

Barone, K.Siobhan; Jain, Shilpa L.; Michael, J.Gabriel

doi:10.1006/cimm.1995.1094

Cited by 71 publications

(43 citation statements)

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“…Weiner and colleagues (20), for example, have provided evidence that both CD4 ϩ and CD8 ϩ T cells play a role in the induction of oral tolerance in EAE and have also postulated the existence of a Th3, TGF-␤-secreting T cell as a mediator in this complex interaction (17). Others (11,21,22) have demonstrated that oral tolerance can be induced in CD8 knockout mice and in mice depleted of CD8 ϩ T cells by anti-CD8 Ab treatment. Thus, it appears that the generation of CD8 ϩ regulatory cells may be sufficient for, but not essential to, the development of oral tolerance.…”

Section: Discussionmentioning

confidence: 99%

Oral Exposure to Alloantigen Generates Intragraft CD8+ Regulatory Cells

Zhou

Carr

Liwski

et al. 2001

The Journal of Immunology

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We have previously reported that oral administration of allogeneic rat spleen cells before kidney allotransplantation significantly prolongs graft survival. This prolongation was alloantigen specific and was associated with a decrease in graft-infiltrating cells (GIC) and an increase in transcription of IL-4 mRNA in the GIC. In this study increased splenic mixed lymphocyte responses from animals orally exposed to alloantigen before kidney transplantation suggested that the kidney allograft prolongation was not due to a masking of allorecognition, but to an immunomodulation of the immune response. We have assessed GIC T cell subsets on day 5 post-transplant and found decreased numbers of CD4+ T cells in fed animals compared with controls, but there was no change in CD8+ T cell numbers. The CD8+ GIC from fed animals transcribed substantial levels of perforin, granzyme, and Fas ligand mRNA, indicating the presence of active CTL. Direct CTL assays showed that the GIC from fed recipients exhibited higher allo-CTL activity than GIC from control unfed recipients. In addition, the CD8+ GIC exhibited high levels of IL-4 mRNA, suggesting Tc2-type regulatory cells. Prolonged graft survival in the face of active CTL and Tc2 cells suggests the presence of a CD8+ regulatory cell population in the allograft. To confirm this, cell transfer experiments were performed. Prolongation of graft survival was transferred from rats orally exposed to alloantigen to naive animals by transfer of CD8+ GIC. This is the first report that oral exposure to alloantigen prolongs kidney allograft survival by the generation of intragraft CD8+ regulatory cells.

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Section: Discussionmentioning

confidence: 99%

Oral Exposure to Alloantigen Generates Intragraft CD8+ Regulatory Cells

Zhou

Carr

Liwski

et al. 2001

The Journal of Immunology

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“…These reports demonstrate that CD8 + lymphocytes can play a regulatory role in a number of immune activities either through classical cytotoxic effects on APC or via the production of cytokines such as IFN-γ and TGF-ß. However, other authors have shown that in vivo depletion of CD8 + cells at the time of feeding had no effect on the induction of oral tolerance, whereas depletion of CD4 + cells completely abolished the suppression of DTH and the antibody response (75,76). It has been suggested that cytokines secreted by special subsets of CD4 + T cells (Th1 and Th2) are involved.…”

Section: Suppression Does Not Imply a Differential Activation Of Th1 mentioning

confidence: 99%

Aging and immunoglobulin isotype patterns in oral tolerance

Faria

Ficker

Speziali

et al. 1998

Braz J Med Biol Res

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In the present review we address oral tolerance as an important biological phenomenon and discuss how it is affected by aging. Other factors such as frequency of feeding and previous digestion of the antigen also seem to influence the establishment of oral tolerance. We also analyze immunoglobulin isotypes of specific antibodies formed by tolerant and immunized animals of different ages submitted to different conditions of oral antigen administration. Isotypic patterns were studied as a parameter for assessing the pathways of B and T cell interactions leading to antibody production.

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“…Recent studies in experimental systems of both oral tolerance (3)(4)(5) and inflammatory bowel disease (6) have underscored the importance of mucosal CD4 ϩ lymphocyte responses. Because the surface expression of class II molecules is essential in cells capable of functioning as antigen-presenting cells (APCs) to CD4 ϩ T cells (7), it is noteworthy that numerous reports have described the low level of HLA class II antigens on the surface of normal IEC and the increased expression of these molecules in a variety of pathological conditions, including inflammatory bowel disease (8), graft-versus-host disease (9), and Celiac disease (10).…”

Section: Introductionmentioning

confidence: 99%