Suppression of T cells specific for the nonthymic parental H-2 haplotype in thymus-grafted chimeras.

Abstract

The mechanism of restriction of T-cell specificity by the genotype of the thymus in allogeneic and semiallogeneic chimeras was investigated. Lack of induction of delayed-type hypersensitivity (DTH) directed against antigen in association with the nonthymic parental haplotype in naive cells adoptively transferred into chimeras suggests the existence of an in vivo suppressive mechanism. However, it was not possible to suppress the expression of DTH in sensitized cells transferred into chimeras, or to transfer this suppression to normal naive recipients.

Bone marrow-derived thymic antigen-presenting cells determine self-recognition of Ia-restricted T lymphocytes.

“…It is possible that more complex mechanisms are at work in the radiation-induced bone marrow chimera that account for the apparent host restriction (21). Smith and Miller (21) have suggested that priming of nonhost parentrestricted T cells is specifically suppressed in F1 * P chimeras.…”

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

“…This selection hypothesis does not, however, provide an adequate explanation for the capacity of nude mice grafted with allogeneic thymus glands to mount a CTL response restricted for the host haplotype, nor does it readily explain the variability in responsiveness of F1 nude mice implanted with parental thymus glands. 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.…”

Incomplete Tolerance to MHC Antigens in Irradiation Chimeras: Implications for MHC Restriction and Self Tolerance

“…§ As for Table I. R antigens in the host thymus. Thus far, attempts to demonstrate suppression of anti-P2 (R or R + X) Tc cells have been unsuccessful (Zinkernagel & Doherty 1979, Blanden & Andrew, unpublished), although suppression has been reported for Td cells by Smith & Miller (1980), In view of clear evidence for suppression in states of neonatally-induced tolerance to MHC antigens in mice (Gorczynski & MacRae 1979) and rats (Dorsch & Roser 1977), these failures are surprising.…”

“…Contradictory evidence also exists concerning the R antigen specificity of T cells that mediate delayed hypersentitivity or helper effects (Miller et al 1979, Smith & Miller 1980, Sprent 1978, Katz et al 1979. It seems likely that their development pathway shares common features with Tc cells, although their R antigens are determined by the / region of the murine H-2 gene complex instead of the K and D regions relevant to Tc cell recognition.…”