{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:34:35Z","timestamp":1791272075735,"version":"4.1.0"},"reference-count":0,"publisher":"Rockefeller University Press","issue":"2","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1994,2,1]]},"abstract":"<jats:p>Transplantation of HLA mismatched hematopoietic stem cells in patients with severe combined immunodeficiency (SCID) can result in a selective engraftment of T cells of donor origin with complete immunologic reconstitution and in vivo tolerance. The latter may occur in the absence of clonal deletion of donor T lymphocytes able to recognize the host HLA antigens. The activity of these host-reactive T cells is suppressed in vivo, since no graft-vs. -host disease is observed in these human chimeras. Here it is shown that the CD4+ host-reactive T cell clones isolated from a SCID patient transplanted with fetal liver stem cells produce unusually high quantities of interleukin 10 (IL-10) and very low amounts of IL-2 after antigen-specific stimulation in vitro. The specific proliferative responses of the host-reactive T cell clones were considerably enhanced in the presence of neutralizing concentrations of an anti-IL-10 monoclonal antibody, suggesting that high levels of endogenous IL-10 suppress the activity of these cells. These in vitro data correlate with observations made in vivo. Semi-quantitative polymerase chain reaction analysis carried out on freshly isolated peripheral blood mononuclear cells (PBMC) of the patient indicated that the levels of IL-10 messenger RNA (mRNA) expression were strongly enhanced, whereas IL-2 mRNA expression was much lower than that in PBMC of healthy donors. In vivo IL-10 mRNA expression was not only high in the T cells, but also in the non-T cell fraction, indicating that host cells also contributed to the high levels of IL-10 in vivo. Patient-derived monocytes were found to be major IL-10 producers. Although no circulating IL-10 could be detected, freshly isolated monocytes of the patient showed a reduced expression of class II HLA antigens. However, their capacity to stimulate T cells of normal donors in primary mixed lymphocyte cultures was within the normal range. Interestingly, similar high in vivo IL-10 mRNA expressions in the T and non-T cell compartment were also observed in three SCID patients transplanted with fetal liver stem cells and in four SCID patients transplanted with T cell-depleted haploidentical bone marrow stem cells. Taken together, these data indicate that high endogenous IL-10 production is a general phenomenon in SCID patients in whom allogenic stem cell transplantation results in immunologic reconstitution and induction of tolerance. Both donor T cells and host accessory cells contribute to these high levels of IL-10, which would suppress the activity of host-reactive T cell in vivo.<\/jats:p>","DOI":"10.1084\/jem.179.2.493","type":"journal-article","created":{"date-parts":[[2004,6,24]],"date-time":"2004-06-24T07:56:10Z","timestamp":1088063770000},"page":"493-502","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":347,"title":["High levels of interleukin 10 production in vivo are associated with tolerance in SCID patients transplanted with HLA mismatched hematopoietic stem cells."],"prefix":"10.1084","volume":"179","author":[{"given":"R","family":"Bacchetta","sequence":"first","affiliation":[{"name":"Human Immunology Department, DNAX Research Institute, Palo Alto, California 94303-1104."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Bigler","sequence":"additional","affiliation":[{"name":"Human Immunology Department, DNAX Research Institute, Palo Alto, California 94303-1104."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J L","family":"Touraine","sequence":"additional","affiliation":[{"name":"Human Immunology Department, DNAX Research Institute, Palo Alto, California 94303-1104."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Parkman","sequence":"additional","affiliation":[{"name":"Human Immunology Department, DNAX Research Institute, Palo Alto, California 94303-1104."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P A","family":"Tovo","sequence":"additional","affiliation":[{"name":"Human Immunology Department, DNAX Research Institute, Palo Alto, California 94303-1104."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Abrams","sequence":"additional","affiliation":[{"name":"Human Immunology Department, DNAX Research Institute, Palo Alto, California 94303-1104."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"de Waal Malefyt","sequence":"additional","affiliation":[{"name":"Human Immunology Department, DNAX Research Institute, Palo Alto, California 94303-1104."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J E","family":"de Vries","sequence":"additional","affiliation":[{"name":"Human Immunology Department, DNAX Research Institute, Palo Alto, California 94303-1104."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M G","family":"Roncarolo","sequence":"additional","affiliation":[{"name":"Human Immunology Department, DNAX Research Institute, Palo Alto, California 94303-1104."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1994,2,1]]},"container-title":["The Journal of experimental medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/179\/2\/493\/1675186\/493.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/179\/2\/493\/1675186\/493.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T05:05:41Z","timestamp":1690261541000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/179\/2\/493\/57542\/High-levels-of-interleukin-10-production-in-vivo"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,2,1]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1994,2,1]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.179.2.493","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,2,1]]}}}