Restriction specificities, alloreactivity, and allotolerance expressed by T cells from nude mice reconstituted with H-2-compatible or -incompatible thymus grafts.

Abstract

Congenitally thymusless nude mice that lacked functional T cells were reconstituted with H-2-compatible or -incompatible thymus grafts taken from either fetal, newborn, or adult mice and transplanted under the kidney capsule or subcutaneously. Transplantation with unirradiated fetal (15--17 d) or newborn thymus grafts reconstituted the nude mice as assessed by their subsequent generation of virus-specific cytotoxic T cells in vivo or alloreactive T cells in vitro. The restriction specificity of T cells from homozygous mice was exclusively for the nude host H-2, as shown by direct cytolysis or by cold target competitive inhibition assays. irrespective of whether nude mice were reconstituted with H-2-compatible, semiallogeneic, or H-2-incompatible, unirradiated newborn or fetal thymus grafts (in order of decreasing efficiency of reconstitution). The restriction specificity for the nonhost H-2 of the thymus could not be demonstrated even after primary or secondary sensitization in an infected appropriate F1 environment. These nude mice reconstituted with fetal or newborn grafts were tolerant to the H-2 of the thymus donors. Nude mice transplanted with irradiated adult thymus grafts were reconstituted functionally with syngeneic or semisyngeneic but not with allogeneic thymus grafts. In homozygous nu/nu irradiated heterozygous recipients of F1 thymus grafts, the restriction specificity for the nonhost thymic H-2 could not be elicited upon adoptive sensitization in irradiated and infected F1 heterozygote stimulator mice; in fact, these chimeras' lymphocytes were not tolerant to the nonhost H-2. The discrepancy between the restorative capacity of unirradiated vs. irradiated thymus grafts suggests that precursors of T cells in nude mice can acquire restriction specificity and immunocompetence independently of a conventional, functioning H-2-compatible thymus if exposed to an allogeneic fetal or a newborn thymus that contains functioning thymocytes of donor type but not if reconstituted with an irradiated adult allogeneic thymus.

Committed T lymphocyte stem cells of rats. Characterization by surface W3/13 antigen and radiosensitivity.

“…The higher radiation doses needed for the eradication of host T stem cells than for B stem cells emphasize the need for careful monitoring of residual T cell activity when it is often presumed to be absent, for example in the preparation of B rats or of bone marrow chimeras for H-2-restriction experiments. Unwanted survival of host T cells could explain some of the discrepancies between findings on nude mice and B mice (24). The present results fit the observation that in semiallogeneic chimeras there is a detectable radioresistant host vs. graft component (10).…”

Sendai virus-specific, H-2-restricted cytotoxic T lymphocyte responses of nude mice grafted with allogeneic or semi-allogeneic thymus glands.

“…These results are in agreement with recent results of Zinkernagel et al (3,4), with the notable exception that considerable individual variation in the degree of preferential lysis mediated by CTL from F1 nude mice implanted with parental thymus glands was observed. It is clear that the thymus does not impose an absolute restriction on T cells because precursor T cells that can recognize virus in association with MHC antigens of the parental haplotype not represented in the thymus graft are present in parental Thy ~ F1 nude mice.…”

“…It is clear that the thymus does not impose an absolute restriction on T cells because precursor T cells that can recognize virus in association with MHC antigens of the parental haplotype not represented in the thymus graft are present in parental Thy ~ F1 nude mice. The results available from the three types of thymusgrafted nude mice examined to date, i.e., B Thy ~ A nude (Table I) (4) (Table II) (3,4) are more consistent with the concept that the MHC restriction of CTL is determined by the genotype of the T cells rather than the haplotype of the implanted thymus. In the case of the A Thy or B Thy ~ (A × B)F1 nude mouse, the implanted thymus could select those T cells that were already committed to recognize antigen in association with the MHC antigens of the thymus.…”

“…The possibility also exists that other regulatory mechanisms, e.g., active suppression (8), are operative in some thymus-grafted nude mice which interfere with full maturation of T cells restricted to MHC antigens of the parental haplotype not represented on the grafted thymus. Furthermore, and in contrast to data from the chimera model (1,(9)(10)(11), no evidence exists in the thymus-grafted nude mouse model to suggest that stem cells that mature in an allogeneic (Table I) (4) or semiallogeneic thymus (4) have the ability to recognize antigen in association with MHC antigens not already expressed by the stem cells.…”

Micro-environnement thymique et différenciation des lymphocytes T

“…Il a été montré que les cellules T sont capables de reconnaître un antigène conventionnel lorsqu'il est associé à des antigènes du complexe majeur d'histocompatibilité (MHC) qui sont également présents sur leurs propres membranes (Zinkernagel, 1976). Les cellules souches pénétrant dans le thymus, pourraient acquérir cette restriction H-2 au contact des cellules épithéliales qui portent à leur surface les produits du MHC (Zinkernagel et al, 1980 (Papiernik et Bach, 1979), les signaux ayant pour origine l'épithélium semblent avoir besoin d'un circuit d'amplification. Celui-ci peut être fourni par les interleukines qui sont produites par les cellules thymiques.…”