The influence of thymus on the development of MHC restrictions exhibited by T-helper cells

Waldmann, Herman; Pope, Heather; Beetles, C; Davies, A. J. S.

doi:10.1038/277137a0

Cited by 38 publications

(12 citation statements)

References 14 publications

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“…These Ta molecules are products of the major histocompatibility gene complex and appear to be involved in cell recognition of antigen or in cell-cell interactions (or both). In addition, accessory cells may be involved in the regulation of T-cell differentiation in the thymus (5)(6)(7)(8)(9).…”

mentioning

confidence: 99%

During ontogeny, Ia-bearing accessory cells are found early in the thymus but late in the spleen.

Lu¹,

Beller²,

Unanue³

1980

Proc. Natl. Acad. Sci. U.S.A.

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The ontogeny of Ia-bearing accessory cells was studied in mice. Ia-bearing adherent eells from the thymus, consisting predominantly of macrophages, were found from birth. These adherent cells were able to present antigen, as measured by their ability to induce immune T-cell proliferation.In contrast, Ia-bearing adherent cells from the spleen were not found until the second week of life, and their antigen-presentation function was not present until later. The differential ontogeny of Ia-bearing accessory cells at these sites may be important in both development of immune competence and the restriction of autoimmunity. Nonlymphoid accessory cells are essential in the activation of several mature T-cell functions (1-4). The accessory cells involved are macrophages characterized by membrane expression of Ia molecules. These Ta molecules are products of the major histocompatibility gene complex and appear to be involved in cell recognition of antigen or in cell-cell interactions (or both). In addition, accessory cells may be involved in the regulation of T-cell differentiation in the thymus (5-9).We have reported recently that, in comparison to adult mice, the peritoneal exudate from neonatal mice contains small numbers of Ia-bearing macrophages. These exudate cells have a corresponding inability to present antigen to immune T cells (10). We report now that, in contrast to these findings, the thymus contains Ia-bearing, antigen-presenting accessory cells from birth. The ontogeny of Ia-bearing accessory spleen cells was also examined; it was similar to the ontogeny of Ia-bearing peritoneal macrophages. MATERIALS AND METHODSA/J, C57BL/6J, and B10.A SgSn adult mice were purchased from The Jackson Laboratory. Neonatal B10.A SgSn, ATL, and C57BL/6J mice were bred in our colony.Because of their low number in the thymus, thymic adherent cells were concentrated on discontinuous bovine serum albumin gradients as described (9). By direct counts, essentially all thymic adherent cells from adult and neonatal mice were found in the low-density fraction banding between 10 and 24% albumin. In both neonatal and adult mice, this low-density fraction contained 3-6% of all thymus cells.The antigen-presentation function of adherent spleen and thymus cells from mice of various ages was evaluated in culture by measuring their ability, after uptake of heat-killed Listeria monocytogenes, to stimulate Listeria-immune T-cell proliferation. Splenocytes or low-density thymus cells from mice of different ages were suspended in RPMI 1640 supplemented with 5% fetal calf serum, antibiotics, 0.5 mM sodium pyruvate, 2 mM L-glutamine, and 0.75% sodium bicarbonate. The cells were then placed in 1.0 X 0.7 cm2, flat-bottom tissue-culture

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mentioning

confidence: 99%

During ontogeny, Ia-bearing accessory cells are found early in the thymus but late in the spleen.

Lu¹,

Beller²,

Unanue³

1980

Proc. Natl. Acad. Sci. U.S.A.

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“…The results described here and elsewhere (28,29) with thymic chimeras represent examples of preference in the sense that higher responses are obtained with certain cell mixtures than with others. The significant qualitative difference between true restriction, on the one hand, and preference, as seen with thymic chimeras, on the other underscores the importance of extrathymic influences on helper T-cell adaptive differentiation.…”

Section: Discussionmentioning

confidence: 52%

“…Secondly, the fact that we find only marginal or sometimes no thymic influence on preference of helper T-cell activity whereas others seem to observe more influence of the thymus (28,29) could reflect the choice of thymic chimeras used for such analyses. Thus, as pointed out in Materials and Methods, we carefully screened all thymic chimeras for functional reconstitution according to their abilities to develop essentially normal anti-KLH antibody responses, an excellent criterion, we believe, for establishing whether KLH-specific helper T-cell activity has been restored to normal levels.…”

Section: Discussionmentioning

confidence: 71%

“…Consistent with this interpretation are the studies of Kindred (26,27) who has reproducibly failed to find evidence of intrathymic learning in nude mice grafted with allogeneic thymuses. As this manuscript was being completed, the observations of Waldmann et al (28) and Bevan and Fink (29), which both concern the effects of thymus grafts on development of H-2 restrictions in helper T-cell functions, appeared in print. Both of these studies were interpreted as indicating a more definite thymic influence on helper T-cell differentiation than reported in the present paper.…”

Section: Discussionmentioning

confidence: 99%

“…Because we discarded those chimeras which developed lower-than-normal anti-KLH responses, we may have selected for those helper T cells which had passed through all stages of the normal T-cell differentiation pathway and hence, been influenced by both intra-and extrathymic events. In the other studies in these systems (1,2,5,7,28,29), comparable functional criteria were not employed as guidelines for selecting the thymic chimeras actually employed and this could very well account for some of the differences in results obtained.…”

Section: Discussionmentioning

confidence: 99%

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Adaptive differentiation of murine lymphocytes. II. The thymic microenvironment does not restrict the cooperative partner cell preference of helper T cells differentiating in F1 leads to F1 thymic chimeras.

Katz¹,

Katz²,

Bogowitz³

et al. 1979

The Journal of Experimental Medicine

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This study was conducted to analyze the extent to which the major histocompatibility complex (MHC) a genotype of the thymus restricts the cooperating phenotype of helper T cells with respect to their ultimate ability to interact effectively with partner B lymphocytes in the development of antibody responses. These studies, like others reported previously (I, 2), made use of artificially constructed bone marrow chimeras prepared by reconstituting aduh-thymectomized, lethally irradiated F1 mice with syngeneic F1 bone marrow, together with transplanted thymuses from either F1 or parental donors. Reconstituted mice of these types were then immunized with keyhole limpet hemocyanin (KLH) and their KLH-specific helper T cells so induced were tested for the cooperative helper activity they could provide to 2,4-dinitrophenyl (DNP)-primed B lymphocytes derived from conventional F1 or parental donors in developing secondary anti-DNP antibody responses to DNP-KLH. The results clearly show that the thymus influences little, and certainly does not restrict, the partner cell preference displayed by helper T cells differentiating in such environments. Moreover, the extent of thymic influence differed depending on the class of antibody being produced with the help of such cells.This investigation is an extension of earlier studies in this (3) and other laboratories (4-10) which have addressed the predictions of the concept of adaptive differentiation (3,(11)(12)(13)(14). This notion ascribes the partner cell preferences of various cells of the lymphoid system, known to be genetically controlled by various regions of the MHC (15), to processes of selection that occur early during cell differentiation and which are determined by the MHC phenotype of the environment in which such differentiation occurs (3,(11)(12)(13)(14). The first experiments supporting this concept were performed * Publication 94 from the Department of Cellular and Developmental Immunology and publication

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Restoration of antibody responsiveness in early thymectomized Xenopus by implantation of major histocompatibility complex‐mismatched larval thymus

Pasquier¹,

Horton

1982

Eur J Immunol

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The restorative potential of isogeneic and fully allogeneic thymic implants to restore in vivo antibody responsiveness to a thymus-dependent antigen has been examined in thymectomized clawed toads. Isogeneic clones (Xenopus laevis/gilli and X. laevis/muelleri hybrids) of known major histocompatability complex (MHC) haplotypes were thymectomized at 5-7 days, implanted with MHC-identical or -mismatched (normal or irradiated ) thymuses from 5-week-old larvae and 4 months later injected with dinitrophenylated keyhole limpet hemocyanin. IgM antibody responsiveness (measured by phage inactivation) was restored in terms of its quantity, affinity and specificity in those thymectomized animals given two haplotype-different thymuses. Isoelectric focusing data revealed that low molecular weight antibody production was also restored with isogeneic and allogeneic thymus and that the antibody spectrotypes were of the host type. The finding that in vivo T-B collaboration in thymectomized animals develops normally following thymus implantation, even when the thymus genotype is disparate from the host, is discussed both in the light of previous experiments revealing MHC restriction of Xenopus T helper cells in vitro and in terms of the role of the thymus in promoting adaptive differentiation of this lymphocyte subset.

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The influence of thymus on the development of MHC restrictions exhibited by T-helper cells

Cited by 38 publications

References 14 publications

During ontogeny, Ia-bearing accessory cells are found early in the thymus but late in the spleen.

During ontogeny, Ia-bearing accessory cells are found early in the thymus but late in the spleen.

Adaptive differentiation of murine lymphocytes. II. The thymic microenvironment does not restrict the cooperative partner cell preference of helper T cells differentiating in F1 leads to F1 thymic chimeras.

Restoration of antibody responsiveness in early thymectomized Xenopus by implantation of major histocompatibility complex‐mismatched larval thymus

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