Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Dec 15;90(24):11718–11722. doi: 10.1073/pnas.90.24.11718

Age-dependent appearance of non-major histocompatibility complex-restricted helper T cells.

C Russo 1, E P Cherniack 1, A Wali 1, M E Weksler 1
PMCID: PMC48055  PMID: 8265615

Abstract

T cells which recognize antigen in association with self major histocompatibility complex (MHC) molecules are positively selected within the thymus. This results in skewing of the T-cell repertoire toward the recognition of antigenic peptides presented by self MHC molecules. While the thymus gland involutes at a relatively young age, bone marrow function and the size of the peripheral T-cell pool are maintained with age. We have investigated the MHC restriction of helper T-cell function for B-cell production of specific antibody in mice of different ages. Splenic helper T cells from 2- to 3-month old mice immunized with phosphocholine-keyhole limpet hemocyanin conjugate were MHC-restricted as defined by their capacity to induce phosphocholine-specific antibody synthesis by syngeneic but not by allogeneic B cells. In contrast, splenic T cells from immunized 18- to 20-month-old mice induced specific anti-phosphocholine antibodies by both syngeneic and allogeneic B cells. No evidence of polyclonal immunoglobulin synthesis was detected. The ability of T cells from old mice immunized with phosphocholine-keyhole limpet hemocyanin to induce phosphocholine-specific antibody synthesis by B cells from allogeneic mice was inhibited by T cells from immunized young mice. These findings suggest that non-MHC-restricted T-cell helper activity in old mice results from the loss of T cells, present in young mice, which suppress non-MHC-restricted helper cells.

Full text

PDF
11718

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bechtol K. B., Freed J. H., Herzenberg L. A., McDevitt H. O. Genetic control of the antibody response to poly-L(Tyr,Glu)-poly-D,L-Ala--poly-L-Lys in C3H--CWB tetraparental mice. J Exp Med. 1974 Dec 1;140(6):1660–1675. doi: 10.1084/jem.140.6.1660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bill J., Palmer E. Positive selection of CD4+ T cells mediated by MHC class II-bearing stromal cell in the thymic cortex. Nature. 1989 Oct 19;341(6243):649–651. doi: 10.1038/341649a0. [DOI] [PubMed] [Google Scholar]
  3. Blackman M. A., Marrack P., Kappler J. Influence of the major histocompatibility complex on positive thymic selection of V beta 17a+ T cells. Science. 1989 Apr 14;244(4901):214–217. doi: 10.1126/science.2784868. [DOI] [PubMed] [Google Scholar]
  4. Bluestone J. A., Cron R. Q., Cotterman M., Houlden B. A., Matis L. A. Structure and specificity of T cell receptor gamma/delta on major histocompatibility complex antigen-specific CD3+, CD4-, CD8- T lymphocytes. J Exp Med. 1988 Nov 1;168(5):1899–1916. doi: 10.1084/jem.168.5.1899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bonneville M., Ito K., Krecko E. G., Itohara S., Kappes D., Ishida I., Kanagawa O., Janeway C. A., Murphy D. B., Tonegawa S. Recognition of a self major histocompatibility complex TL region product by gamma delta T-cell receptors. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5928–5932. doi: 10.1073/pnas.86.15.5928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Calabi F., Milstein C. A novel family of human major histocompatibility complex-related genes not mapping to chromosome 6. Nature. 1986 Oct 9;323(6088):540–543. doi: 10.1038/323540a0. [DOI] [PubMed] [Google Scholar]
  7. Chesebro B., Metzger H. Affinity labeling of a phosphorylcholine binding mouse myeloma protein. Biochemistry. 1972 Feb 29;11(5):766–771. doi: 10.1021/bi00755a014. [DOI] [PubMed] [Google Scholar]
  8. Christmas S. E. Most human CD3+WT31- clones with T cell receptor C gamma 1 rearrangements show strong non-MHC-restricted cytotoxic activity in contrast to those with C gamma 2 rearrangements. Eur J Immunol. 1989 Apr;19(4):741–746. doi: 10.1002/eji.1830190426. [DOI] [PubMed] [Google Scholar]
  9. DeKruyff R. H., Kim Y. T., Siskind G. W., Weksler M. E. Age related changes in the in vitro immune response: increased suppressor activity in immature and aged mice. J Immunol. 1980 Jul;125(1):142–147. [PubMed] [Google Scholar]
  10. Diaz-Jauanen E., Strickland R. G., Williams R. C. Studies of human lymphocytes in the newborn and the aged. Am J Med. 1975 May;58(5):620–628. doi: 10.1016/0002-9343(75)90497-0. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Fisch P., Malkovsky M., Braakman E., Sturm E., Bolhuis R. L., Prieve A., Sosman J. A., Lam V. A., Sondel P. M. Gamma/delta T cell clones and natural killer cell clones mediate distinct patterns of non-major histocompatibility complex-restricted cytolysis. J Exp Med. 1990 May 1;171(5):1567–1579. doi: 10.1084/jem.171.5.1567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gearhart P. J., Sigal N. H., Klinman N. R. Heterogeneity of the BALB/c antiphosphorylcholine antibody response at the precursor cell level. J Exp Med. 1975 Jan 1;141(1):56–71. doi: 10.1084/jem.141.1.56. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gerber V., Ponnappan U., Heusser C. H., Blaser K., Cinader B. Age- and strain-dependent polymorphism in IgE antibody against the phosphorylcholine hapten. Eur J Immunol. 1986 Jun;16(6):713–716. doi: 10.1002/eji.1830160621. [DOI] [PubMed] [Google Scholar]
  15. Goidl E. A., Innes J. B., Weksler M. E. Immunological studies of aging. II. Loss of IgG and high avidity plaque-forming cells and increased suppressor cell activity in aging mice. J Exp Med. 1976 Oct 1;144(4):1037–1048. doi: 10.1084/jem.144.4.1037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gorczynski R. M., Kennedy M., MacRae S. Altered lymphocyte recognition repertoire during ageing. III. Changes in MHC restriction patterns in parental T lymphocytes and diminution in T suppressor function. Immunology. 1984 Aug;52(4):611–620. [PMC free article] [PubMed] [Google Scholar]
  17. Gottesman S. R., Walford R. L., Thorbecke G. J. Proliferative and cytotoxic immune functions in aging mice. II. Decreased generation of specific suppressor cells in alloreactive cultures. J Immunol. 1984 Oct;133(4):1782–1787. [PubMed] [Google Scholar]
  18. Happ M. P., Kubo R. T., Palmer E., Born W. K., O'Brien R. L. Limited receptor repertoire in a mycobacteria-reactive subset of gamma delta T lymphocytes. Nature. 1989 Dec 7;342(6250):696–698. doi: 10.1038/342696a0. [DOI] [PubMed] [Google Scholar]
  19. Hedrick S. M., Matis L. A., Hecht T. T., Samelson L. E., Longo D. L., Heber-Katz E., Schwartz R. H. The fine specificity of antigen and Ia determinant recognition by T cell hybridoma clones specific for pigeon cytochrome c. Cell. 1982 Aug;30(1):141–152. doi: 10.1016/0092-8674(82)90020-4. [DOI] [PubMed] [Google Scholar]
  20. Hooper B., Whittingham S., Mathews J. D., Mackay I. R., Curnow D. H. Autoimmunity in a rural community. Clin Exp Immunol. 1972 Sep;12(1):79–87. [PMC free article] [PubMed] [Google Scholar]
  21. Ishii N., Baxevanis C. N., Nagy Z. A., Klein J. Responder T cells depleted of alloreactive cells react to antigen presented on allogeneic macrophages from nonresponder strains. J Exp Med. 1981 Sep 1;154(3):978–982. doi: 10.1084/jem.154.3.978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ito K., Van Kaer L., Bonneville M., Hsu S., Murphy D. B., Tonegawa S. Recognition of the product of a novel MHC TL region gene (27b) by a mouse gamma delta T cell receptor. Cell. 1990 Aug 10;62(3):549–561. doi: 10.1016/0092-8674(90)90019-b. [DOI] [PubMed] [Google Scholar]
  23. Kennedy D. W., Russo C., Kim Y. T., Weksler M. E. T cell proliferation induced by anti-self-I-A-specific T cell hybridomas. Evidence of a T cell network. J Exp Med. 1986 Aug 1;164(2):490–500. doi: 10.1084/jem.164.2.490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kishimoto S., Tomino S., Mitsuya H., Fujiwara H., Tsuda H. Age-related decline in the in vitro and in vivo syntheses of anti-tetanus toxoid antibody in humans. J Immunol. 1980 Nov;125(5):2347–2352. [PubMed] [Google Scholar]
  25. Leo O., Foo M., Sachs D. H., Samelson L. E., Bluestone J. A. Identification of a monoclonal antibody specific for a murine T3 polypeptide. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1374–1378. doi: 10.1073/pnas.84.5.1374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Makinodan T., Kay M. M. Age influence on the immune system. Adv Immunol. 1980;29:287–330. doi: 10.1016/s0065-2776(08)60047-4. [DOI] [PubMed] [Google Scholar]
  27. Piguet P. F., Vassalli P. Collaboration between histoincompatible T and B lymphocytes: preferential induction in vivo of antibodies to antigens borne by foreign T cells. J Immunol. 1981 Oct;127(4):1304–1307. [PubMed] [Google Scholar]
  28. Porcelli S., Brenner M. B., Greenstein J. L., Balk S. P., Terhorst C., Bleicher P. A. Recognition of cluster of differentiation 1 antigens by human CD4-CD8-cytolytic T lymphocytes. Nature. 1989 Oct 5;341(6241):447–450. doi: 10.1038/341447a0. [DOI] [PubMed] [Google Scholar]
  29. Reimann J., Miller R. G. Rapid changes in specificity within single clones of cytolytic effector cells. Cell. 1985 Mar;40(3):571–581. doi: 10.1016/0092-8674(85)90205-3. [DOI] [PubMed] [Google Scholar]
  30. Reinherz E. L., Kung P. C., Goldstein G., Schlossman S. F. Separation of functional subsets of human T cells by a monoclonal antibody. Proc Natl Acad Sci U S A. 1979 Aug;76(8):4061–4065. doi: 10.1073/pnas.76.8.4061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Riley S. C., Froscher B. G., Linton P. J., Zharhary D., Marcu K., Klinman N. R. Altered VH gene segment utilization in the response to phosphorylcholine by aged mice. J Immunol. 1989 Dec 1;143(11):3798–3805. [PubMed] [Google Scholar]
  32. Rádl J., Hollander C. F. Homogeneous immunoglobulins in sera of mice during aging. J Immunol. 1974 Jun;112(6):2271–2273. [PubMed] [Google Scholar]
  33. Schwab R., Russo C., Weksler M. E. Altered major histocompatibility complex-restricted antigen recognition by T cells from elderly humans. Eur J Immunol. 1992 Nov;22(11):2989–2993. doi: 10.1002/eji.1830221134. [DOI] [PubMed] [Google Scholar]
  34. Sprent J., Lo D., Gao E. K., Ron Y. T cell selection in the thymus. Immunol Rev. 1988 Jan;101:173–190. doi: 10.1111/j.1600-065x.1988.tb00737.x. [DOI] [PubMed] [Google Scholar]
  35. Terhorst C., van Agthoven A., LeClair K., Snow P., Reinherz E., Schlossman S. Biochemical studies of the human thymocyte cell-surface antigens T6, T9 and T10. Cell. 1981 Mar;23(3):771–780. doi: 10.1016/0092-8674(81)90441-4. [DOI] [PubMed] [Google Scholar]
  36. Thoman M. L., Weigle W. O. Deficiency in suppressor T cell activity in aged animals. Reconstitution of this activity by interleukin 2. J Exp Med. 1983 Jun 1;157(6):2184–2189. doi: 10.1084/jem.157.6.2184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Thomas D. W., Shevach E. M. Nature of the antigenic complex recognized by T lymphocytes: specific sensitization by antigens associated with allogeneic macrophages. Proc Natl Acad Sci U S A. 1977 May;74(5):2104–2108. doi: 10.1073/pnas.74.5.2104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Vidović D., Roglić M., McKune K., Guerder S., MacKay C., Dembić Z. Qa-1 restricted recognition of foreign antigen by a gamma delta T-cell hybridoma. Nature. 1989 Aug 24;340(6235):646–650. doi: 10.1038/340646a0. [DOI] [PubMed] [Google Scholar]
  39. Waldmann H., Pope H., Munro A. J. Cooperation across the histocompatibility barrier. Nature. 1975 Dec 25;258(5537):728–730. doi: 10.1038/258728a0. [DOI] [PubMed] [Google Scholar]
  40. Weltzien H. U., Kempkes B., Studer R., Melchers I., Eichmann K. Growth-dependent variation of major histocompatibility complex (MHC) restriction and expression of Ly-2 and CD3/alpha/beta T cell receptor in cloned cytotoxic T cells. Eur J Immunol. 1988 Mar;18(3):431–437. doi: 10.1002/eji.1830180317. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES