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Immunology Today, vol. 5, No. 6, 1984

R] (,...,. } T-cell regulation of IgA responses SIR, Charles Elson (Immunol. Today, 1983, Vol. 4, pp. 189-190) and Charles Janeway, J r (Immunol. Today, 1983, Vol. 4, pp. 335-336) have discussed the likelihood that the IgA response in mice is regulated by isotype-specific helper and suppressor T lymphocytes. The following in-vitro studies provide evidence for the occurrence of IgA-specific helper T

cells for polyclonally induced B-cell activation in man. An 11-month-old male child presented with multiple congenital abnormalities, hypoealcaemia and a history of clinical sepsis, suggestive of partial DiGeorge syndrome. However, T- and B-cell numbers, serum immunoglobulin levels, proliferative responses to phytohaemagglutinin (PHA) and concanavalin A (Con A), and O K T 4 / O K T 8 ratios were all substantially normal. Using a protein A haemolytic plaque assay and pokeweed mitogen (PWM) stimulation of peripheral blood mononuclear cells (PBM) to investigate B-cell function, we found a profound deficiency of IgG, IgA and IgM plaque-forming cells (PFC)

TABLE I. Analysis of B-cell function and helper T-cell function in a patient with partial DiGeorge syndrome. PBM preparation incubated with PWM

Patient

PFC/106 cells cultured Control

IgG lgA IgM IgG Normal values 2 750-24 000 Unfractionated 0 0 240 6 200 OKT8-depleted 0 0 0 13 200 AC-depleted 0 0 0 5 100 OKT4-depleted 400 Control OKT4 + patient's OKT4 + 400 2 100 600 E-FRC ÷ 0 Control E-RFC* + patient'sAC-E-RFC- 3840 960 2880

Mechanisms in chronic inflammation SIR, Whicher and Chambers (Immunol. Today 1984, Vol. 4, pp. 3-4) discussed some mechanisms which might explain chronic inflammation in rheumatoid disease. Another mechanism may lie in the link between the immunoregulatory activity of the circulating protease inhibitor a 2 - macroglobulin (a2M) and that of the acute phase protein a I - proteinase inhibitor (aPi)1-5. a2M activates B cells in vitro but also suppresses a variety of the functions of immunocompetent cells ~. This suppressive activity is increased after c o m plex formation with protease, and work from our centre indicates it is associated with liberation of low molecular weight peptide which is itself immunosuppressire 2. Biochemically, a2M accepts pro-

IgA 1 700-19 000 3 100 9 600 2 210 400 0

IgM 2 750-35 000 6 510 15 900 4 050 800

(see Table I). Depletion of OKT8 ÷ or adherent cells (AC) failed to reverse the deficiency, but significant numbers of IgG and IgM PFC appeared in PWMstimulated co-cultures of control sheep erythroeyte (E) rosette-forming cells (E-RFC ÷) with the patient's AC , E - R F C - cells, though IgA-producing cells remained below normal levels. Interestingly, when control OKT4depleted PBM (non-responsive to PWM-induced B-cell activation) were cultured with the patient's purified O K T 4 + PBM, significant numbers of IgA PFC appeared, but there were no IgG or IgM PFC. It appeared therefore that the inability of the patient's PBM to produce IgA after P W M stimulation was due to a B-cell defect, whereas failure to produce IgG and IgM was due to a lack of T help for these isotypes, IgA-specific T helper function being intact. While isotype-specific B-cell defects have been recognized for many years, this may be the first demonstration of isotype-specific helper T-cell deficiency in man.

BRIAN M. JONES

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tease fl'om the other major plasma protease inhibitor a 1Pi which, because of its low molecular weight, readily penetrates synovial fluid 3, alPi itself has immunoregulatory activity, perhaps by blocking lymphocyte surface protease 4. Since alPi is oxidized and inactivated by free radicals 5 it is possible that as a result of inflammatory change, alPi accumulates in the synovial fluid to block protease but is itself inactivated by excess radicals exposed when phagocytes release protease, a2M, which has also been identified in joint fluid, may then be preferentially complexed with protease. The resultant suppression of lymphocyte function in this medium would favour cellular accumulation without inflammatory resolution and subsequent cell death would contribute to further radical release. The control mechanism would then be related to the activity and turnover within the joint of

Clinical Immunology Unit, Department of Pathology, University of Hong Kong, Hong Kong. the acute phase protein aPi, which is well known to be raised in the sera of rheumatoid patients. This mechanism of chronic inflammation may have application beyond that of rheumatoid disease. P. K. DONNELLY B. K. SHENTON Department of Surgery, The University of Newcastle upon Tyne, The Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP~ UK. References l James, K. (1980) Trends in Biochem. Sci. 5, 43-47. 2 Donnelly,P. K., Shenton, B. K., Alomran, A., Francis D. M. A., Proud, G. and Taylor, R. M. R. (1983) Br. J. Surg. 70, 614-622 3 Beatty,K., Travis, J. and Bieth, J. (1982) Biochem. Biophys. Aaa 704, 221-226 4 Bata, J. and Revillard, J. (1981) AgentS Actions 11,614--616 5 Matheson,N. R., Janoff, A. and Travis, J. (1982) Mol. Cell. Biochem. 45, 65-71

Mechanisms in chronic inflammation.

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