Autoreactive T cell clones specific for class I and class II HLA antigens isolated from a human chimera

T cell clones of donor origin that specifically react with recipient cells were obtained from a SCID patient successfully reconstituted by allogeneic fetal liver and thymus transplantation performed 10 yr ago. The majority of these clones displayed both cytotoxic and proliferative responses towards PBL and an EBV-transformed B cell line derived from the patient. In addition, these T cell clones had proliferative and cytotoxic responses towards the parental PBL, EBV cell lines, and PHA blasts. Blocking studies with anti-class I and anti-class II HLA mAbs indicated that the activity of the CD4+ T cell clones was specifically directed against class II HLA antigens of the recipient. On the other hand, the cytotoxic and proliferative responses of the CD8+ T cell clones were specific for class I HLA antigens which are ubiquitously expressed on the recipient cells. Thus, the establishment of transplantation tolerance observed in this stable human chimera is not due to the elimination of host-reactive T cells from the repertoire and suggests the presence of a peripheral autoregulatory suppressor mechanism.

[1]  A. Hill,et al.  Quantitative Considerations of T‐Cell Activation and Self Tolerance , 1987, Immunological reviews.

[2]  N. Flomenberg,et al.  Autocytotoxic and autosuppressor T-cell lines generated from autologous lymphocyte cultures. , 1987, Human immunology.

[3]  P. Marrack,et al.  T cell tolerance by clonal elimination in the thymus , 1987, Cell.

[4]  S. Strober,et al.  Cloned natural suppressor cells prevent lethal graft-vs-host disease. , 1987, Journal of immunology.

[5]  J. Levy,et al.  Autoreactive T cell clones of MHC class II specificities are produced during responses against foreign antigens in man. , 1987, Journal of immunology.

[6]  I. Hutchinson.  Suppressor T cells in allogeneic models. , 1986, Transplantation.

[7]  R. Geha,et al.  Induction of IgG and IgE synthesis in normal B cells by autoreactive T cell clones. , 1986, Journal of immunology.

[8]  J. Margolick,et al.  The production and characterization of thyroid-derived T-cell lines in Graves' disease and Hashimoto's thyroiditis. , 1986, Clinical immunology and immunopathology.

[9]  R. Miller.  The veto phenomenon and T-cell regulation. , 1986, Immunology today.

[10]  J. Banchereau,et al.  Cooperation between major histocompatibility complex mismatched mononuclear cells from a human chimera in the production of antigen-specific antibody. , 1986, The Journal of clinical investigation.

[11]  M. Feldmann,et al.  Human T-cell clones from autoimmune thyroid glands: specific recognition of autologous thyroid cells. , 1985, Science.

[12]  W. V. van Blitterswijk,et al.  Serum-free medium for generation and propagation of functional human cytotoxic and helper T cell clones. , 1984, Journal of immunological methods.

[13]  R. Hohlfeld,et al.  Autoimmune human T lymphocytes specific for acetylcholine receptor , 1984, Nature.

[14]  E. Reinherz,et al.  Delineation of an immunoregulatory amplifier population recognizing autologous Ia molecules. Analysis with human T cell clones , 1984, The Journal of experimental medicine.

[15]  J. Touraine.  Bone‐Marrow and Fetal‐Liver Transplantation in Immunodeficiencies and Inborn Errors of Metabolism: Lack of Significant Restriction of T‐Cell Function in Long‐Term Chimeras Despite HLA‐Mismatch , 1983, Immunological reviews.

[16]  H. Bétuel,et al.  Immunodeficiency diseases and expression of HLA antigens. , 1981, Human immunology.

[17]  V. Quaranta,et al.  Purification of immunologically functional subsets of human Ia-like antigens on a monoclonal antibody (Q5/13) immunoadsorbent. , 1980, Journal of immunology.

[18]  I. Hilgert.  The Involvement of Activated Specific Suppressor T Cells in Maintenance of Transplantation Tolerance , 1979, Immunological reviews.

[19]  R. Zinkernagel,et al.  On the thymus in the differentiation of "H-2 self-recognition" by T cells: evidence for dual recognition? , 1978, The Journal of experimental medicine.

[20]  T. Miyazaki,et al.  Characterization studies of suppressor cells in murine bone marrow chimaeras. , 1987, Immunology.

[21]  J. Soulillou.  Functional characteristics of cells infiltrating rejected allografts. , 1987, Immunology today.

[22]  C. Griscelli,et al.  Self Education after Mismatched HLA Haploidentical Bone Marrow Transplantation , 1985 .

[23]  B. Dupont,et al.  Transplantation of hematopoietic cells for lethal congenital immunodeficiencies. , 1983, Birth defects original article series.

[24]  L. Gebuhrer,et al.  A possible new HLA-DR allele. , 1983, Human immunology.

[25]  J. Borst,et al.  Characterization of monoclonal antibodies against cell surface molecules associated with cytotoxic activity of natural and activated killer cells and cloned CTL lines. , 1983, Hybridoma.