Skip to main content
Log in

T helper cell dysfunction in systemic lupus erythematosus (SLE): Relation to disease activity

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

Abstract

Patients with systemic lupus erythematosus (SLE) are known to have defects in both humoral and cellular immunity. The significance of defective T cell-mediated immunity and its relationship to disease activity have not been clearly established. We studiedin vitro T helper cell (Th) function in 150 SLE outpatients and correlated Th function with validated measures of disease activity. Interleukin 2 (IL-2) production by peripheral blood mononuclear cells (PBMC) was measured after stimulation with the recall antigens influenza A virus (FLU) and tetanus toxoid (TET), irradiated allogeneic peripheral blood mononuclear cells (ALLO), and phytohemagglutinin (PHA). We observed three patterns of Th response: (1) 76 of 150 (50%) of patients responded to the recall antigens FLU and/or TET, ALLO, and PHA; (2) 62 of 150 (42%) of patients did not respond to recall antigens but responded to ALLO and PHA; and (3) 12 of 150 (8%) of patients did not respond to either recall antigens or ALLO antigens. This diminished T cell function was correlated with higher disease activity as measured by four scales of clinical activity, such that individuals who exhibited morein vitro immune dysfunction presented with significant increases in their clinical activity indicies. The alterations in T cell function could not be accounted for by medication doses alone. Thus, SLE patients have multiple distinct defects at the level of the Th cell which are associated with clinical measures of disease activity.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Via CS, Tsokos G, Shearer GM: Defective MHC-self restricted T helper cell function is a feature of both murine and human lupus. Arth Rheum 32:S133, 1989 (abstr)

    Google Scholar 

  2. Tsokos GC, Balow JE: Cellular immune responses in systemic lupus erythematosus. Prog Allergy 35:93–161, 1984

    PubMed  Google Scholar 

  3. Tsokos GC, Balow JE: Spontaneous and pokeweed mitogen-induced plaque-forming cells in systemic lupus erythematosus. Clin Immunol Immunopathol 21:172–183, 1981

    PubMed  Google Scholar 

  4. Schmitt C, Cogne M, Agrapart M, Ballet JJ: Major histo-compatibility complex restriction of tetanus toxoid-specific human T lymphocyte clones. Eur J Immunol 14:1131–1136, 1984

    PubMed  Google Scholar 

  5. Lamb JR, Eckels DE, Lake P, Johnson AH, Hartzman RJ, Woody JN: Antigen-specific human T lymphocyte clones: induction, antigen specificity, and MHC restriction of influenza virus-immune clones. J Immunol 128:233–238, 1982

    PubMed  Google Scholar 

  6. Alcocer-Varela J, Alarcon-Segovia D: Decreased production of and response to interleukin-2 by cultured lymphocytes from patients with systemic lupus erythematosus. J Clin Invest 69:1388–1392, 1982

    PubMed  Google Scholar 

  7. Draeger AM, Swaak AJ, Van Der Brink HG, Aarden LA: T Cell function in systemic lupus erythematosus: normal production of and responsiveness to interleukin-2. Clin Exp Immunol 64:80–87, 1986

    PubMed  Google Scholar 

  8. Brozek CM, Hoffman LA, Savage SM, Searles RP: Systemic lupus erythematosus sera inhibit antigen presentation by macrophages to T cells. Clin Immunol Immunopathol 46:299–313, 1988

    PubMed  Google Scholar 

  9. Shirakawa F, Yamashita U, Suzuki H: Decrease in HLA-DR-positive monocytes in patients with systemic lupus erythematosus. J Immunol 134:3560–3562, 1985

    PubMed  Google Scholar 

  10. Smolen JS, Chusid TM, Leiserson WM, Reeves JP, Alling DA, Steinberg AD: Heterogeneity of immunoregulatory T-cell subsets in systemic lupus erythematosus. Am J Med 72:783–790, 1982

    PubMed  Google Scholar 

  11. Bakke AC, Kirkland PA, Kitridou RC, Quismorio Jr. FP, Rea T, Ehrismann GR, Horwitz DA: T lymphocyte subsets in systemic lupus erythematosus. Arth Rheum 26:745–750, 1983

    Google Scholar 

  12. Linker-Israeli M, Bakke A, Quisimorio F, Horwitz D: Correction of interleukin-2 production in patients with systemic lupus erythematosus by removal of spontaneously activated suppressor cells. J Clin Invest 75:762–768, 1985

    PubMed  Google Scholar 

  13. Via CS, Tsokos GC, Stocks NI, Clerici M, Shearer GM: Human in vitro allogeneic responses: Demonstration of three pathways of T helper cell activation. J Immunol 144:2524–2528, 1990

    PubMed  Google Scholar 

  14. Clerici M, Stocks NI, Zajac RA, Boswell RN, Lucey DR, Via CS, Shearer GM: Detection of three distinct patterns of T helper cell dysfunction in asymptomatic, Human Immunodeficiency Virus-seropositive patients. J Clin Invest 84:1892–1899, 1989

    PubMed  Google Scholar 

  15. Clerici M, Shearer GM: Differential sensitivity of human T helper cell pathways by in vitro exposure to cyclosporin A. J Immunol 144:2480–2485, 1990

    PubMed  Google Scholar 

  16. Maluk SC, Clerici M, Via CS, Weir MR, Kimmel PL, Shearer GM: Correlation of in vitro CD4+ T helper cell function with clinical graft status in immunosuppressed kidney transplant recipients. Transplantation 52:284–289, 1991

    PubMed  Google Scholar 

  17. Via CS, Tsokos GC, Bermas BL, Clerici M, Shearer GM: T cell antigen presenting cell interactions in human systemic lupus: Evidence for heterogenous expression of multiple defects. J Immunol, 151:3914–3922, 1993

    PubMed  Google Scholar 

  18. Lucey DR, Melcher GP, Hendrix CW, Zajac RA, Goetz DW, Butzin CA, Clerici M, Warner RD, Abbadessa S, Hall S, Jose R, Woolford B, Miller S, Stocks NI, Salinas CM, Wolfe WH, Shearer GM, and Boswell RN: Human immunodeficiency infection in the US Air Force: Seroconversion, clinical staging and assessment of a T helper cell functional assay to predict change in CD4+ T cell counts. J Infect Diseases 64:631–637, 1991

    Google Scholar 

  19. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller J, Talal N, Winchester RJ: The 1982 revised criteria for the classification of systemic lupus erythematosus. Arth Rheum 25:1271–1277, 1982

    Google Scholar 

  20. Petri M, Hellmann D, Hochberg M: Validity and reliability of lupus activity measures in the routine clinic setting. J Rheum 19:53–59, 1992

    PubMed  Google Scholar 

  21. Uchiyama T, Broder S, Waldmann TA: A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. J Immunol 126:1393–1397, 1981

    PubMed  Google Scholar 

  22. Beverly PC, Michie CA, Young JL: Memory and the lifespan of human T lymphocytes. Leukemia 7 (Suppl 2):550–554, 1993

    Google Scholar 

  23. Van Der Horst DA, Van der Marel A, den Ottolander GJ: Decrease in memory T helper cells (CD4+CD45RO+) in hairy cell leukemia. Leukemia 7:46–50, 1993

    PubMed  Google Scholar 

  24. Gordon C, Schlesinger B, Mathews N, Palen P, Salmon M, Emery P: Active SLE: Evidence for recruitment from virgin T cells and implications for therapy. Arth Rheum 36 (Suppl):5183, 1993

    Google Scholar 

  25. Clerici M, Hakim FT, Venzon DJ, Blatt S, Hendrix CW, Wynn TA, Shearer GM: Changes in interleukin 2 and interleukin 4 production in asymptomatic, HIV-seropositive individual. J Clin Invest 91:759–765, 1993

    PubMed  Google Scholar 

  26. Linker-Israeli M, Deans RJ, Wallace DJ, Prehn J, Ozeri-Chen T, Klinenberg JR: Elevated levels of endogenous IL-6 in systemic lupus erythematosus: A putative role in pathogenesis. J Immunol 147:117–123, 1991

    PubMed  Google Scholar 

  27. Clerici M, Shearer GM: A TH1-TH2 switch is a critical step in the etiology of HIV infection. Immunol Today 14:107–111, 1993

    PubMed  Google Scholar 

  28. Harrison LC, Honeyman MC, De Aizpurua HI, Schmidli RS, Colman PG, Tait BD, Cram DS: Inverse relation between humoral and cellular immunity to gluatamic acid decarboxylase in subjects at risk of insulin-dependent diabetes. Lancet 341:1365–1367, 1993

    PubMed  Google Scholar 

  29. Griffin DE, Ward BJ: Differential CD4 T cell activation in measles. J Infect Dis 168:275–281, 1993

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bermas, B.L., Petri, M., Goldman, D. et al. T helper cell dysfunction in systemic lupus erythematosus (SLE): Relation to disease activity. J Clin Immunol 14, 169–177 (1994). https://doi.org/10.1007/BF01533366

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01533366

Key words

Navigation