Selective modulation of T-cell immunity by intrathymic cellular transplantation (original) (raw)
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Pediatrics International, 1991
We have observed two patients who exhibited an exclusive increase of 6TCSl' subset of y6 T cells in the peripheral blood after bone marrow transplantation (BMT). In one case with severe combined immunodeficiency (SCID) who received haploidentical BMT from his father, y6 T cells appeared only after thymus transplantation. However, his T cell-mediated immunity remained severely defective despite the generation of T cells of donor origin. In the other case with aplastic anemia, 6TCSl-y6 T cells began to increase in the peripheral blood later. This indicates that the thymus is necessary for the generation of y6 T cells and that the 6TCS1+ subset is dominant in the early stages of their ontogeny. GTCS1' T cell lines were established from both patients, and allo-reactivity was investigated. The cell Line from the latter case reacted to recipient cells in a mixed lymphocyte reaction, but did not show cytotoxity to the allogeneic cells including recipient cells. The other cell line, from the former case, did not react to either donor or recipient cells. This indicates that an intact thymus is needed for y6 T cells to acquire allo-reactivity . Both cell lines showed MHC non-restricted cytotoxity against NKsensitive target cells. only in small numbers among peripheral blood T cells [ 2 ] . However, they exist in larger numbers in the skin [3-51 and in the mucosa of the intestine [6] , and are considered t o play a primitive defense role in tissues affected by the invasion of foreign bodies [7,. Their ontogeny is mostly thymus-dependent [9], but some undergo extrathymic development [9, 101 . They have been shown to have MHC-restricted [ll-141 and unrestricted [15-181 cytotoxic activity. The most recent reports indicate that y6 TCR+cells perform important functions in immune reactions against specific agents, such
Antigen-Specific CD3 +, CD4 -, CD8 - T Lymphocytes
Most antigen-specific peripheral murine T lymphocytes express the T cell differentiation antigens, CD4 or CD8, and a TCR composed ofa CD3-associated disulfidelinked heterodimer, TCR-a/(3 (1, 2). However, recent studies have identified a distinct population of CD3+,CD4-,CD8-cells that appear early in thymic ontogeny and are maintained in the mature thymus and the peripheral lymphoid organs throughout adult life . Immunoprecipitation studies of murine CD3 +,CD4-, CD8-T cells have shown that the majority of these cells do not express cell surface TCR a/a; rather their TCR complex includes a 45-kD S glycoprotein disulfide linked to either the TCRV y/Cylt gene product or the TCRV y/Cy4 gene product (demonstrated by immunoprecipitation with anti TCRy antisera) (5-7). These results suggested that the TCR-, y/8' cells may compose a separate lineage that develops in the thymus before the TCRa/R-expressing T cells .
Immunology, 2008
We studied the tolerization of neonatal thymocytes (NT), neonatal splenocytes (NS) and adult thymocytes (AT), transferred to syngeneic nude (nu/nu) hosts previously injected with semi-allogeneic splenocytes, without any supportive immunosuppressive treatment. This protocol allows the study of peripheral tolerance in the absence of the thymus. BALB/c neonatal T cells and ATs were able to expand in syngeneic BALB/ c nu/nu mice and functionally reconstituted an allogeneic response, rejecting (BALB/c • B6.Ba) F1 splenocytes transferred 3-4 weeks after injection of BALB/c cells. However, if (BALB/c • B6.Ba) F1 cells were injected into BALB/c nude hosts 30 days before transfer of NT, NS or AT cells, the F1 population was preserved and specific tolerance to B6 allografts was established. Furthermore, transfer to lymphopenic F1 nu/nu showed that tolerance could be established only for neonatal populations, showing that unique properties of neonatal T cells allow their tolerization in both lymphopenic and non-lymphopenic conditions, in the absence of suppressive immunotherapy. These results bring empirical support to the possibility of T-cell engraftment in immunodeficient patients showing partial identity with donor major histocompatibility complex (MHC) genes; the manipulation of immunological maturity of donor T cells may be the key for successful reconstitution of immunocompetence without induction of graft-versus-host disease.