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J Exp Med. 1986 September 1; 164(3): 911–925.
PMCID: PMC2188395

Long-term humoral unresponsiveness in vivo, induced by treatment with monoclonal antibody against L3T4


mAbs directed against the L3T4 molecule administered in vivo caused a severe and long lasting helper cell depletion in mice. Regeneration of the L3T4+ subpopulation occurred gradually (2-3 mo) after a single antibody treatment. Experiments were designed to examine the humoral immunocompetence of such anti-L3T4-treated animals during and after regeneration of the L3T4+ T cell subset. The animals were injected with anti-L3T4, immunized with soluble antigen, and challenged with antigen every 2 wk. Antibody responses to two antigens, sperm whale myoglobin (SpWMb) and KLH, which differ with regard to their immunogenicity, were compared. The lack of humoral immune responsiveness to either of these two antigens shorty after anti-L3T4 treatment responsiveness to either of these two antigens shortly after anti-L3T4 treatment was probably due to clonal depletion. The anti-L3T4-induced immunosuppressive effect on antibody production seemed to be determined in part by the preexisting T cell repertoire, as was suggested by the recovery of responsiveness to the highly immunogenic antigen KLH and the transient inhibitory effect of anti-L3T4 treatment in primed animals. The regenerating L3T4+ T cell subpopulation was relatively incompetent in initiating B cell responses. More than 40% of the L3T4+ T cell compartment had to recover to provide help for the production of anti- KLH antibodies, whereas elimination of 90% of the L3T4+ helper cells did not inhibit a primary anti-KLH response. Evidence for a heterogeneous composition of the L3T4+ subset came from experiments using rIL-2 in vivo. The addition of rIL-2 during early helper cell depletion improved the recovery of the humoral responsiveness without apparently affecting the kinetics of the regeneration of L3T4+ T cells. Interestingly, humoral unresponsiveness to the weakly immunogenic antigen SpWMb persisted for at least 120 d. This long lasting unresponsiveness could not be explained by clonal depletion, and suggested as one possibility that the presence of antigen during regeneration of the L3T4+ helper cell population may have influenced the ultimate T cell repertoire.

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Selected References

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  • Cosimi AB, Colvin RB, Burton RC, Rubin RH, Goldstein G, Kung PC, Hansen WP, Delmonico FL, Russell PS. Use of monoclonal antibodies to T-cell subsets for immunologic monitoring and treatment in recipients of renal allografts. N Engl J Med. 1981 Aug 6;305(6):308–314. [PubMed]
  • Wofsy D, Ledbetter JA, Hendler PL, Seaman WE. Treatment of murine lupus with monoclonal anti-T cell antibody. J Immunol. 1985 Feb;134(2):852–857. [PubMed]
  • Waldor MK, Sriram S, Hardy R, Herzenberg LA, Herzenberg LA, Lanier L, Lim M, Steinman L. Reversal of experimental allergic encephalomyelitis with monoclonal antibody to a T-cell subset marker. Science. 1985 Jan 25;227(4685):415–417. [PubMed]
  • Wofsy D, Seaman WE. Successful treatment of autoimmunity in NZB/NZW F1 mice with monoclonal antibody to L3T4. J Exp Med. 1985 Feb 1;161(2):378–391. [PMC free article] [PubMed]
  • Cobbold SP, Jayasuriya A, Nash A, Prospero TD, Waldmann H. Therapy with monoclonal antibodies by elimination of T-cell subsets in vivo. Nature. 1984 Dec 6;312(5994):548–551. [PubMed]
  • Fabre JW, Sunderland CA, Williams AF. Immunosuppressive properties of mouse monoclonal antibodies and rabbit antisera to a leukocyte-specific antigen in the rat. Transplant Proc. 1981 Mar;13(1 Pt 1):509–511. [PubMed]
  • Ritz J, Schlossman SF. Utilization of monoclonal antibodies in the treatment of leukemia and lymphoma. Blood. 1982 Jan;59(1):1–11. [PubMed]
  • Dialynas DP, Quan ZS, Wall KA, Pierres A, Quintáns J, Loken MR, Pierres M, Fitch FW. Characterization of the murine T cell surface molecule, designated L3T4, identified by monoclonal antibody GK1.5: similarity of L3T4 to the human Leu-3/T4 molecule. J Immunol. 1983 Nov;131(5):2445–2451. [PubMed]
  • Wilde DB, Marrack P, Kappler J, Dialynas DP, Fitch FW. Evidence implicating L3T4 in class II MHC antigen reactivity; monoclonal antibody GK1.5 (anti-L3T4a) blocks class II MHC antigen-specific proliferation, release of lymphokines, and binding by cloned murine helper T lymphocyte lines. J Immunol. 1983 Nov;131(5):2178–2183. [PubMed]
  • Golding H, McCluskey J, Munitz TI, Germain RN, Margulies DH, Singer A. T-cell recognition of a chimaeric class II/class I MHC molecule and the role of L3T4. Nature. 1985 Oct 3;317(6036):425–427. [PubMed]
  • Nossal GJ. Cellular mechanisms of immunologic tolerance. Annu Rev Immunol. 1983;1:33–62. [PubMed]
  • Klinman NR, Press JL. The characterization fo the B-cell repertoire specific for the 2,4-dinitrophenyl and 2,4,6-trinitrophenyl determinants in neonatal BALB/c mice. J Exp Med. 1975 May 1;141(5):1133–1146. [PMC free article] [PubMed]
  • Etlinger HM, Heusser CH. Expression of a distinct B cell clonotype profile after recovery from antigen-induced unresponsiveness. Eur J Immunol. 1982 Jun;12(6):530–533. [PubMed]
  • Thompson MA, Raychaudhuri S, Cancro MP. Restricted adult clonal profiles induced by neonatal immunization. Influence of suppressor T cells. J Exp Med. 1983 Jul 1;158(1):112–125. [PMC free article] [PubMed]
  • Ledbetter JA, Rouse RV, Micklem HS, Herzenberg LA. T cell subsets defined by expression of Lyt-1,2,3 and Thy-1 antigens. Two-parameter immunofluorescence and cytotoxicity analysis with monoclonal antibodies modifies current views. J Exp Med. 1980 Aug 1;152(2):280–295. [PMC free article] [PubMed]
  • Goding JW. Conjugation of antibodies with fluorochromes: modifications to the standard methods. J Immunol Methods. 1976;13(3-4):215–226. [PubMed]
  • Hayakawa K, Hardy RR, Parks DR, Herzenberg LA. The "Ly-1 B" cell subpopulation in normal immunodefective, and autoimmune mice. J Exp Med. 1983 Jan 1;157(1):202–218. [PMC free article] [PubMed]
  • Shigeta M, Takahara S, Knox SJ, Ishihara T, Vitetta ES, Fathman CG. Two independent pathways of helper activity provided by a single T cell clone. J Immunol. 1986 Jan;136(1):34–38. [PubMed]
  • Weyand CM, Goronzy J, Dallman MJ, Fathman CG. Administration of recombinant interleukin 2 in vivo induces a polyclonal IgM response. J Exp Med. 1986 Jun 1;163(6):1607–1612. [PMC free article] [PubMed]
  • Wofsy D, Mayes DC, Woodcock J, Seaman WE. Inhibition of humoral immunity in vivo by monoclonal antibody to L3T4: studies with soluble antigens in intact mice. J Immunol. 1985 Sep;135(3):1698–1701. [PubMed]
  • Coulie PG, Coutelier JP, Uyttenhove C, Lambotte P, Van Snick J. In vivo suppression of T-dependent antibody responses by treatment with a monoclonal anti-L3T4 antibody. Eur J Immunol. 1985 Jun;15(6):638–640. [PubMed]
  • Jefferies WA, Green JR, Williams AF. Authentic T helper CD4 (W3/25) antigen on rat peritoneal macrophages. J Exp Med. 1985 Jul 1;162(1):117–127. [PMC free article] [PubMed]
  • Sproviero JF, Imperiale MJ, Zauderer M. Clonal analysis of F1 hybrid helper T cells. I-A subregion-encoded hybrid determinants restrict the activity of keyhole limpet hemocyanin-specific helper T cells. J Exp Med. 1981 Oct 1;154(4):1255–1260. [PMC free article] [PubMed]

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