Abstract
Thymus-derived lymphocytes (T cells) have two outstanding characteristics that distinguish them from other lymphocytes: (a) they express two specificities, one for self-antigens, the major transplantation antigens (H) coded by the major histocompatibility gene complex (MHC), and a second specificity for foreign antigenic determinants. (b) T cells must undergo differentiation or maturation in the thymus (1, 2). Apparently, an important step in T-cell differentiation in the thymus is the selection of T-cells’ restriction specificity for self-H. This interpretation stems from experiments with chimeras formed by lethally irradiating parental type mice and reconstituting them with F(1) stem cells: the maturing F(1) T cells expressed predominantly the restriction specificities for the recipient parental MHC type (3-8). Alternatively, adult F(1) mice that were thymectomized, lethally irradiated, reconstituted with bone marrow, and then engrafted with a parental thymus had T cells that were restricted predominantly to the thymus donors' H-2 (4-8). The present study first extends these observations to nude mice that are born without a thymus and therefore do not develop functional T cells and second, attempts to study the possibility that suppression may be responsible for the apparent influence of the radioresistant portion of the thymus on T- cell restriction specificities. We tested the immunocompetence and restriction specificities expressed by lymphocytes from F(1) nude mice reconstituted with both parental thymus grafts; our expectation was that suppression of the expression of T-cell restriction specificity should result either in complete immunoincompetence or emergence of only one of the two possible sets of restriction specificities. Nude F(1)mice that simultaneously received thymus gratis from both parents developed spleen cells restricted to both parental H-2 types. These results are compatible with the idea that the thymus’ influence on T- cell restriction is via positive selection rather than by suppression.
Full Text
The Full Text of this article is available as a PDF (313.9 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bennink J. R., Doherty P. C. T-cell populations specifically depleted of alloreactive potential cannot be induced to lyse H-2-different virus-infected target cells. J Exp Med. 1978 Jul 1;148(1):128–135. doi: 10.1084/jem.148.1.128. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bevan M. J. In a radiation chimaera, host H-2 antigens determine immune responsiveness of donor cytotoxic cells. Nature. 1977 Sep 29;269(5627):417–418. doi: 10.1038/269417a0. [DOI] [PubMed] [Google Scholar]
- Bevan M. J. Killer cells reactive to altered-self antigens can also be alloreactive. Proc Natl Acad Sci U S A. 1977 May;74(5):2094–2098. doi: 10.1073/pnas.74.5.2094. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blanden R. V., Andrew M. E. Primary anti-viral cytotoxic T-cell responses in semiallogeneic chimeras are not absolutely restricted to host H-2 type. J Exp Med. 1979 Feb 1;149(2):535–538. doi: 10.1084/jem.149.2.535. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Callahan G. N., Ferrone S., Poulik M. D., Reisfeld R. A., Klein J. Characterization of Ia antigens in mouse serum. J Immunol. 1976 Oct;117(4):1351–1355. [PubMed] [Google Scholar]
- Davies A. J. The thymus and the cellular basis of immunity. Transplant Rev. 1969;1:43–91. doi: 10.1111/j.1600-065x.1969.tb00136.x. [DOI] [PubMed] [Google Scholar]
- Doherty P. C., Bennink J. C. Vaccinia-specific cytotoxic T-cell responses in the context of H-2 antigens not encountered in thymus may reflect aberrant recognition of a virus-H-2 complex. J Exp Med. 1979 Jan 1;149(1):150–157. doi: 10.1084/jem.149.1.150. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kindred B., Loor F. Activity of host-derived T cells which differentiate in nude mice grafted with co-isogenic or allogeneic thymuses. J Exp Med. 1974 May 1;139(5):1215–1227. doi: 10.1084/jem.139.5.1215. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Matzinger P., Mirkwood G. In a fully H-2 incompatible chimera, T cells of donor origin can respond to minor histocompatibility antigens in association with either donor or host H-2 type. J Exp Med. 1978 Jul 1;148(1):84–92. doi: 10.1084/jem.148.1.84. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miller J. F., Gamble J., Mottram P., Smith F. I. Influence of thymus genotype on acquisition of responsiveness in delayed-type hypersensitivity. Scand J Immunol. 1979;9(1):29–38. doi: 10.1111/j.1365-3083.1979.tb02703.x. [DOI] [PubMed] [Google Scholar]
- Miller J. F., Osoba D. Current concepts of the immunological function of the thymus. Physiol Rev. 1967 Jul;47(3):437–520. doi: 10.1152/physrev.1967.47.3.437. [DOI] [PubMed] [Google Scholar]
- Watson J., Epstein R., Nakoinz I., Ralph P. The role of humoral factors in the initiation of in vitro primary immune responses. II. Effects of lymphocyte mitogens. J Immunol. 1973 Jan;110(1):43–52. [PubMed] [Google Scholar]
- Wilson D. B., Lindahl K. F., Wilson D. H., Sprent J. The generation of killer cells to trinitrophenyl-modified allogeneic targets by lymphocyte populations negatively selected to strong alloantigens. J Exp Med. 1977 Aug 1;146(2):361–367. doi: 10.1084/jem.146.2.361. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zinkernagel R. M., Althage A., Cooper S., Callahan G., Klein J. In irradiation chimeras, K or D regions of the chimeric host, not of the donor lymphocytes, determine immune responsiveness of antiviral cytotoxic T cells. J Exp Med. 1978 Sep 1;148(3):805–810. doi: 10.1084/jem.148.3.805. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zinkernagel R. M., Callahan G. N., Althage A., Cooper S., Klein P. A., Klein J. On the thymus in the differentiation of "H-2 self-recognition" by T cells: evidence for dual recognition? J Exp Med. 1978 Mar 1;147(3):882–896. doi: 10.1084/jem.147.3.882. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zinkernagel R. M. Thymus and lymphohemopoietic cells: their role in T cell maturation in selection of T cells' H-2-restriction-specificity and in H-2 linked Ir gene control. Immunol Rev. 1978;42:224–270. doi: 10.1111/j.1600-065x.1978.tb00264.x. [DOI] [PubMed] [Google Scholar]
