Abstract
Fetal liver and thymus transplantation can be successfully employed for the treatment of severe combined immunodeficiency disease. In virtually all cases, donor and recipient cells are HLA mismatched. In a patient suffering from a severe combined immunodeficiency disease, full immunological reconstitution was obtained after fetal liver and thymus transplantation. HLA typing revealed that the patient's T cells were of donor origin, while the B cells and monocytes were of host origin. Despite this complete HLA mismatch, the patient was found to mount a subnormal to normal antibody response in vivo. This finding is in contrast with the concept that antigen recognition by T cells is major histocompatibility complex (MHC) restricted. To define the mechanism responsible for this in vivo antibody response, antibody production by peripheral blood mononuclear cells from the patient was tested in vitro after in vivo booster. The in vitro anti-tetanus toxoid antibody production was similar to that of the control group. In addition, specific proliferative responses to tetanus toxoid were obtained. Immunoglobulin allotype determination showed that antibodies were synthetized by host B cells. The results of the present study indicate that transplanted T lymphocytes and recipient cells cooperate despite complete HLA mismatch.
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Selected References
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- Benveniste E., Stevens R. H. T suppressor cells are required for the maintenance of the antigen-induced B-cell unresponsive state in humans. J Clin Immunol. 1983 Apr;3(2):166–172. doi: 10.1007/BF00915488. [DOI] [PubMed] [Google Scholar]
- Betuel H., Gebuhrer L., Lambert J., Freidel A. C., Farre A. A possible new HLA-DR allele. Hum Immunol. 1983 Nov;8(3):227–237. doi: 10.1016/0198-8859(83)90040-x. [DOI] [PubMed] [Google Scholar]
- Brenner M. K., North M. E. Human B cell growth factors overcome T cell-mediated inhibition of specific antibody production: a possible mechanism for the exacerbation of autoimmune disease. Clin Exp Immunol. 1983 Jun;52(3):635–640. [PMC free article] [PubMed] [Google Scholar]
- Callard R. E., McCaughan G. W., Babbage J., Souhami R. L. Specific in vitro antibody responses by human blood lymphocytes: apparent nonresponsiveness of PBL is due to a lack of recirculating memory B cells. J Immunol. 1982 Jul;129(1):153–156. [PubMed] [Google Scholar]
- Chu E., Umetsu D., Rosen F., Geha R. S. Major histocompatibility restriction of antigen recognition by T cells in a recipient of haplotype mismatched human bone marrow transplantation. J Clin Invest. 1983 Sep;72(3):1124–1129. doi: 10.1172/JCI111037. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Geha R. S. Dynamics of human circulating antigen reactive cells following secondary immunization with tetanus toxoid. Clin Immunol Immunopathol. 1981 May;19(2):196–205. doi: 10.1016/0090-1229(81)90063-5. [DOI] [PubMed] [Google Scholar]
- Gonwa T. A., Picker L. J., Raff H. V., Goyert S. M., Silver J., Stobo J. D. Antigen-presenting capabilities of human monocytes correlates with their expression of HLA-DS, an Ia determinant distinct from HLA-DR. J Immunol. 1983 Feb;130(2):706–711. [PubMed] [Google Scholar]
- Hünig T., Bevan M. J. Self H-2 antigens influence the specificity of alloreactive cells. J Exp Med. 1980 May 1;151(5):1288–1298. doi: 10.1084/jem.151.5.1288. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ishii N., Baxevanis C. N., Nagy Z. A., Klein J. Responder T cells depleted of alloreactive cells react to antigen presented on allogeneic macrophages from nonresponder strains. J Exp Med. 1981 Sep 1;154(3):978–982. doi: 10.1084/jem.154.3.978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Katz D. H., Hamaoka T., Benacerraf B. Cell interactions between histoincompatible T and B lymphocytes. II. Failure of physiologic cooperative interactions between T and B lymphocytes from allogeneic donor strains in humoral response to hapten-protein conjugates. J Exp Med. 1973 Jun 1;137(6):1405–1418. doi: 10.1084/jem.137.6.1405. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lane H. C., Whalen G., Fauci A. S. Antigen-induced human T cell help. Precursor frequency, radiation sensitivity, and allogeneic effects. J Clin Invest. 1983 Aug;72(2):636–647. doi: 10.1172/JCI111013. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lanzavecchia A., Parodi B., Celada F. Activation of human B lymphocytes: frequency of antigen-specific B cells triggered by alloreactive or by antigen-specific T cell clones. Eur J Immunol. 1983 Sep;13(9):733–738. doi: 10.1002/eji.1830130908. [DOI] [PubMed] [Google Scholar]
- Matzinger P. A one-receptor view of T-cell behaviour. Nature. 1981 Aug 6;292(5823):497–501. doi: 10.1038/292497a0. [DOI] [PubMed] [Google Scholar]
- Mitchell D. M., Beverley P. C., Boyle D. G., Winger L. A., Callard R. E. Accessory cell and HLA compatibility requirements for the generation of specific in-vitro antibody responses to influenza virus by human blood lymphocytes. Immunology. 1983 Oct;50(2):239–250. [PMC free article] [PubMed] [Google Scholar]
- Rivat L., Gilbert D., Ropartz C. Immunoglobulin allotypic specificities in mixed leucocyte cultures. Immunology. 1973 Jun;24(6):1041–1049. [PMC free article] [PubMed] [Google Scholar]
- Singer A., Hodes R. J. Mechanisms of T cell-B cell interaction. Annu Rev Immunol. 1983;1:211–241. doi: 10.1146/annurev.iy.01.040183.001235. [DOI] [PubMed] [Google Scholar]
- Thorsby E. The role of HLA in T cell activation. Hum Immunol. 1984 Jan;9(1):1–7. doi: 10.1016/0198-8859(84)90002-8. [DOI] [PubMed] [Google Scholar]
- Touraine J. L. 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. Immunol Rev. 1983;71:103–121. doi: 10.1111/j.1600-065x.1983.tb01070.x. [DOI] [PubMed] [Google Scholar]
- Touraine J. L., Bétuel H. Immunodeficiency diseases and expression of HLA antigens. Hum Immunol. 1981 Mar;2(2):147–153. doi: 10.1016/0198-8859(81)90061-6. [DOI] [PubMed] [Google Scholar]
- Touraine J. L., Bétuel H. Immunodeficiency diseases and expression of HLA antigens. Hum Immunol. 1981 Mar;2(2):147–153. doi: 10.1016/0198-8859(81)90061-6. [DOI] [PubMed] [Google Scholar]
- Unanue E. R. Antigen-presenting function of the macrophage. Annu Rev Immunol. 1984;2:395–428. doi: 10.1146/annurev.iy.02.040184.002143. [DOI] [PubMed] [Google Scholar]
- Volkman D. J., Allyn S. P., Fauci A. S. Antigen-induced in vitro antibody production in humans: tetanus toxoid-specific antibody synthesis. J Immunol. 1982 Jul;129(1):107–112. [PubMed] [Google Scholar]
- Zinkernagel R. M., Callahan G. N., Althage A., Cooper S., Klein P. A., Klein J. On the thymus in the differentiation of "H-2 self-recognition" by T cells: evidence for dual recognition? J Exp Med. 1978 Mar 1;147(3):882–896. doi: 10.1084/jem.147.3.882. [DOI] [PMC free article] [PubMed] [Google Scholar]
