Skip to main content
SpringerLink
Log in

Equivalent helper functions of human “naive” and “memory” CD4+ T cells for the generation of alloreactive cytotoxic T lymphocytes

  • Original Articles
  • Published:
Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

Cells comprising the CD4+ T-cell population are heterogeneous with regard to function, maturation, and the expression of membrane molecules such as the CD45RA antigen. Previous analyses of the CD4+ subsets defined by CD45RA antigen expression have shown that the ability to provide help for antibody production is restricted to cells within the CD4+CD45RA− subset. In the present studies, we have examined the ability of “naive” CD4+CD45RA+ cells and “memory” CD4+CD45RA− cells to provide help for the generation of alloreactive CD8+ cytotoxic T lymphocytes. When purified CD4+CD45RA+ or CD4+CD45RA− cells were cultured with autologous CD8+ cells and allogeneic E-stimulator cells, both subsets were consistently able to provide help for CD8+ cytotoxic T-cell development. In contrast, the ability to provide help for antibody production was restricted to cells in the CD4+CD45RA− subset. Differences in the mechanisms of the helper functions for these two systems were also identified. Whereas exogenous interleukin-2 (IL-2) could replace the help provided by either CD4+ subset for cytotoxic T-cell generation, IL-2 had only minimal effects on immunoglobulin production. Thus, our studies highlight the contrasting cellular requirements and mechanisms involved in “help” for B-cell differentiation versus cytotoxic T-lymphocyte generation, and they show that the helper/inducer functions of human CD4+ cells are not mediated solely by the CD4+CD45RA− subset.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Gatenby PA, Kansas GS, Xian CY, Evans RL, Engleman EG: Dissection of immunoregulatory subpopulations of T lymphocytes within the helper and suppressor sublineages in man. J Immunol 129:1997–2000, 1982

    Google Scholar 

  2. Reinherz EL, Morimoto C, Fitzgerald KA, Hussey RE, Daley JF, Schlossman SF: Heterogeneity of human T4+ inducer T cells defined by a monoclonal antibody that delineates two functional subpopulations. J Immunol 128:463–470, 1982

    Google Scholar 

  3. Kansas GS, Wood GS, Fishwild DM, Engleman EG: Functional characterization of human T lymphocyte subsets distinguished by monoclonal anti-Leu-8. J Immunol 134:2995–3003, 1985

    Google Scholar 

  4. Tedder TF, Clement LT, Cooper MD: Human lymphocyte differentiation antigens HB-10 and HB-11. I. Ontogeny of antigen expression. J Immunol 134:2983–2988, 1985

    Google Scholar 

  5. Tedder TF, Cooper MD, Clement LT: Human lymphocyte differentiation antigens HB-10 and HB-11. II. Differential production of B cell growth and differentiation factors by distinct helper T cell subpopulations. J Immunol 134:2989–2994, 1985

    Google Scholar 

  6. Mormoto C, Letvin NL, Distaso JA, Aldrich WR, Schlossman SF: The isolation and characterization of the human suppressor inducer T cell subset. J Immunol 134:1508–1513, 1985

    Google Scholar 

  7. Smith SH, Brown MH, Rowe D, Callard RE, Beverly PCL: Functional subsets of human helper-inducer cells defined by a new monoclonal antibody, UCHL1. Immunology 58:63–71, 1986

    Google Scholar 

  8. Streuli M, Hall LR, Saga Y, Schlossman SF, Saito H: Differential usage of three exons generates at least five different mRNAs encoding human leukocyte common antigens. J Exp Med 166:1548–1557, 1987

    Google Scholar 

  9. Mossmann T, Coffman RL: Two types of mouse helper T cell clones. Implications for immune regulation. Immunol Today 8:223–227, 1987

    Google Scholar 

  10. Yefenof E, Sanders VM, Uhr JW, Vitetta ES: In vitro activation of murine antigen-specific memory B cells by a T-dependent antigen. J Immunol 137:85–90, 1987

    Google Scholar 

  11. Bartlett W, Michael A, MacCann J, Yuan D, Claassen E, Noelle RJ: Cognate interactions between helper T cells and B cells. II. Dissection of cognate help by using a class II-restricted antigen-specific, IL-2-dependent helper T cell clone. J Immunol 143:1745–1751, 1989

    Google Scholar 

  12. Landay A, Gartland GL, Clement LT: Characterization of a phenotypically distinct subpopulation of Leu-2+ cells that suppresses T cell proliferative responses. J Immunol 131:2757–2761, 1983

    Google Scholar 

  13. Clement LT, Yamashita N, Martin AM: The functionally distinct subpopulations of human helper/inducer T lymphocytes defined by anti-CD45RA antibodies derive sequentially from a differentiation pathway that is regulated by activation-dependent post-thymic differentiation. J Immunol 141:1464–1470, 1988

    Google Scholar 

  14. Yamashita N, Clement LT: Phenotypic characterization of the post-thymic differentiation of human alloantigen-specific CD8+ cytotoxic T lymphocytes. J Immunol 143:1518–1523, 1989

    Google Scholar 

  15. Clement LT, Dagg MK, Landay A: Characterization of human lymphocyte subpopulations: Alloreactive cytotoxic T lymphocyte precursor and effector cells are phenotypically distinct from Leu-2+ suppressor cells. J Clin Immunol 4:395–402, 1984

    Google Scholar 

  16. Hakkbar AN, Terry L, Timms A, Beverly PCL, Janossy G: Loss of CD45R and gain of UCHL1 reactivity is a feature of primed T cells. J Immunol 140:2171–2176, 1988

    Google Scholar 

  17. Kalish RS, Morimoto C, Schlossman SF, Generation of CD8 (T8) cytotoxic cells has a preferential requirement for CD4 + 2H4− inducer cells. Cell Immunol 111:379–385, 1988

    Google Scholar 

  18. Wee SL, Chen LK, Strassmann G, Bach FH: Helper cell-independent cytotoxic clones in man. J Exp Med 156:1854–1862, 1982

    Google Scholar 

  19. Singer A, Munitz TI, Golding H, Rosenberg AS, Mizuochi T: Recognition requirements for the activation, differentiation, and function of T helper cells specific for class I MHC alloantigens. Immunol Rev 98:143–162, 1987

    Google Scholar 

  20. Mizuochi T, Hugin AW, Morse HC, Singer A, Buller RML: Role of lymphokine-secreting CD8+ T cells in cytotoxic T lymphocyte responses against vaccinia virus. J Immunol 142:270–275, 1989

    Google Scholar 

  21. Sanders ME, Makgoba MW, Shaw S: Human naive and memory T cells: Reinterpretation of helper-inducer and suppressor-inducer subsets. Immunol Today 9:195–199, 1988

    Google Scholar 

  22. Serra HM, Krowka JF, Ledbetter JA, Pilarski LM: Loss of CD45R (Lp220) represents a post-thymic T cell differentiation event. J Immunol 140:1441–1445, 1988

    Google Scholar 

  23. Hirohata S, Lipsky PE: T cell regulation of human B cell proliferation and differentiation. Regulatory influences of CD45R + and CD45R - T4 cell subsets. J Immunol 142:2597–2604, 1989

    Google Scholar 

  24. Moore K, Nesbitt AM: Identification and isolation of OKT4+ suppressor cells with the monoclonal antibody WR16. Immunology 58:659–667, 1986

    Google Scholar 

  25. Gillis S, Gillis AE, Henney CS: Monoclonal antibody directed against interleukin 2. I. Inhibition of T lymphocyte mitogenesis and the in vitro differentiation of alloreactive cytotoxic T cells. J Exp Med 154:983–994, 1981

    Google Scholar 

  26. Wagner H, Hardt C, Rouse BT, Roellinghoff M, Scheurich P, Pfizenmaier K: Dissection of the proliferative and differentiation signals controlling murine cytotoxic T lymphocyte responses. J Exp Med 155:1876–1885, 1982

    Google Scholar 

  27. Chen L, Tourvielle B, Burns GF, Bach FH, Mathieu-Mahul D, Sasportes, M, Bensussan A: Interferon: A cytotoxic T lymphocyte differentiation signal. Eur J Immunol 16:767–771, 1986

    Google Scholar 

  28. Maraskovsky E, Chen WF, Shortman K: IL-2 and IFN-g are two necessary lymphokines in the development of cytolytic T cells. J Immunol 143:1210–1214, 1989

    Google Scholar 

  29. Widmer MB, Grabstein KH: Regulation of cytolytic T-lymphocyte generation by B-cell stimulatory factor. Nature (London) 326:795–797, 1987

    Google Scholar 

  30. Pfeifer JD, Mckenzie DT, Swain SL, Dutton RW: B cell stimulatory factor 1 (interleukin 4) is sufficient for the proliferation and differentiation of lectin-stimulated cytolytic T lymphocyte precursors. J Exp Med 166:1464–1474, 1987

    Google Scholar 

  31. Takatsu K, Kikuchi Y, Takahashi T, Honjo T, Matsumoto M, Harada N, Yamaguchi N, Tominaga A: Interleukin 5, a T-cell derived B-cell differentiation factor also induces cytotoxic T lymphocytes. Proc Natl Acad Sci USA 84:4234–4239, 1987

    Google Scholar 

  32. Takai Y, Wong GG, Clark SC, Burakoff SJ, Hermann SH: B cell stimulatory factor-2 is involved in the differentiation of cytotoxic T lymphocytes. J Immunol 140:508–512, 1988

    Google Scholar 

  33. Okada M, Kitahara M, Kishimoto S, Matsuda T, Hirano T, Kishimoto T: IL-6/BSF-2 functions as a killer helper factor in the in vitro induction of cytotoxic T cells. J Immunol 141:1543–1549, 1988

    Google Scholar 

  34. Uyttenhove C, Coulie PG, van Snick J: T cell growth and differentiation induced by interleukin-HP1/IL-6, the murine hybridoma/plasmacytoma growth factor. J Exp Med 167:1417–1422, 1988

    Google Scholar 

  35. Rosenberg SA, Lotze MT: Cancer immunotherapy using interleukin-2 and interleukin-2-activated lymphocytes. Annu Rev Immunol 4:681–704, 1986

    Google Scholar 

  36. Leist TP, Kohler M, Eppler M, Zinkernagel RM: Effects of treatment with IL-2 receptor specific monoclonal antibody in mice. Inhibition of cytotoxic T cell responses but not of T help. J Immunol 143:628–634, 1989

    Google Scholar 

  37. Sanders ME, Makgoba MW, Sharrow SO, Stephany D, Springer TA, Young HA, Shaw S: Human memory lymphocytes express increased levels of three cell adhesion molecules (LFA-3, CD2, and LFA-1) and three other molecules (UCHL1, CDw29, and Pgp-1) and have enhanced IFN-g production. J Immunol 140:1401–1408, 1988

    Google Scholar 

  38. Clement LT, Roberts RL, Martin AM: Characterization of a monocyte differentiation factor distinct from gamma-interferon, tumor necrosis factor, or G,M-colony stimulating factor that regulates the growth and functional capabilities of the U937 monocytic cell line. J Leuk Biol 44:101–110, 1988

    Google Scholar 

  39. Paliard X, de Waal Malefijt R, Yssel H, Blanchard D, Chretien I, Abrams J, de Vries J, Spits H: Simultaneous production of IL-2, IL-4, and IFN-g by activated human CD4+ and CD8+ T cell clones. J Immunol 141:849–855, 1988

    Google Scholar 

  40. Kashahara T, Hooks JJ, Dougherty SF, Oppenheim JJ: Interleukin 2-mediated immune interferon production by human T cells and T cel subsets. J Immunol 130:1784–1789, 1983

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Microbiology and Immunology, UCLA School of Medicine, 90024, Los Angeles, California

    Naomi Yamashita & Robin Bullington

  2. Department of Pediatrics, UCLA School of Medicine, 90024, Los Angeles, California

    Loran T. Clement

Authors
  1. Naomi Yamashita
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robin Bullington
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Loran T. Clement
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yamashita, N., Bullington, R. & Clement, L.T. Equivalent helper functions of human “naive” and “memory” CD4+ T cells for the generation of alloreactive cytotoxic T lymphocytes. J Clin Immunol 10, 237–246 (1990). https://doi.org/10.1007/BF00916699

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00916699

Key words

Search

Navigation