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TUBERCULIN ANERGY AND INFECTIOUS MONONUCLEOSIS
74
Preliminary
Communications
TUBERCULIN ANERGY AND INFECTIOUS MONONUCLEOSIS S. HAIDER
M. DE L. COUTINHO R. T. D. EMOND
of illness which became positive when they were tested 6 weeks later; five of these eight gave a definite history of B.C.G. vaccination. These results (see table) suggest that in a considerable number of patients (35%) there was a transient depression of cellmediated immunity during the acute phase of infectious mononucleosis:
Royal Free Hospital Infectious Diseases Unit, Coppetts Wood Hospital, London N10 1JN R. N. P. SUTTON
Department of Medical Microbiology, King’s College Hospital Medical School, London SE5 8RX DISCUSSION
Cell-mediated immunity, as assessed Summary by the response to tuberculin, was in investigated twenty-three patients with infectious mononucleosis. In eight patients, negative reactions were observed during acute illness which became positive during convalescence, suggesting that there had been a temporary depression of cell-mediated
immunity. INTRODUCTION
THE recognition that the Epstein-Barr (E.B.) virus is the probable causative agent in infectious mononucleosis 1,2 has led to a resurgence of interest in this disease. Immunologically, the most impressive feature of infectious mononucleosis is the development of a medley of inappropriate " antibodies which are probably, in part at least, responsible for the high levels of immunoglobulins found in this disease.3-5 The humoral limb of the immune response thus remains intact, although functioning somewhat aberrantly. What happens to cell-mediated immunity in the acute phase of infectious mononucleosis is not well documented, apart from one reportof transient depression of the tuberculin response. Tuberculin reactivity is an efferent activity of the T lymphocyte in response to intradermal tuberculin. A positive reaction expresses an intact cell-mediated immunity system in an individual who, in the past, has been exposed to Mycobacterium tuberculosis, and non-reactivity in such a person indicates an abnormality in this system. The conversion from non-reactivity to a reactive state indicates recovery from a transient immunological depression affecting this system. We used this simple test to assess the cell-mediated immunity in infectious mononucleosis. "
The exact mechanism of this transient depression of the cell-mediated immune response is not clear. Is it due to virus multiplication in the T lymphocytes
with consequent functional impairment ? E.B. virus particles are, in vitro, cleared from cultured infectious-mononucleosis leucocytes within 2-3 not but we do know what happens in vivo; months,7,8 can failure of clearance occur and, if so, could it result in continued immunosuppression ? There are further implications of this transient immunological depression in infectious mononucleosis. The association of the herpes-like E.B. virus with infectious mononucleosis, with Burkitt’s lymphoma, and with some types of nasopharyngeal carcinoma is now well recognised.4,9 There have been reports that nucleic acid homologous with that of the R.N.A. Rauscher murine-leukxmia virus has been detected in Burkitt’s tumour and in nasopharyngealThese apparently conflicting carcinoma cells of observations groups may be reconciled if we that of cell-mediated immunity accept depression E.B. virus infection (as in infectious monoby nucleosis) could provide the necessary stimulus to activate an otherwise dormant virus genome.11 The disturbance of cell-mediated immunity in infectious mononucleosis and in the more frequent asymptomatic infections with the E.B. virus deserves further investigation as a possible mechanism for the induction of malignant change in man. We are grateful to Dr Hillas Smith for his permission include some of the patients admitted under his care. Requests for reprints should be addressed to S. H. REFERENCES 1. 2.
PATIENTS AND METHODS
infectious mononucleosis, including heterophile antibodies and typical abnormal white blood-cells, were investigated. All were given an intradermal test of 1/10,000 tuberculin during the acute phase of the illness, and this test was repeated 6 weeks later. The tests were read after 48 hours and an area of induration of 8 mm. or over was considered to be Patients
with
clinical features
of
positive. RESULTS
patients with infectious monoincluded in this survey. Eight gave tuberculin reaction during the acute phase
3. 4. 5. 6.
7. 8. 9. 10.
Twenty-three nucleosis a
negative
were
to
11. 12.
Henle, G., Henle, W., Diehl, V. Proc. natn. Acad. Sci. U.S.A. 1968, 59, 94. Niedermann, J. C., Evans, A. S., Subrahmanyan, L., McCollum, R. W. New Engl. J. Med. 1970, 282, 361. Wollheim, F. A., Williams, R. C. ibid. 1966, 274, 61. Sutton, R. N. P. J. clin. Path. 1972, 25, suppl. 6, p. 58. Sutton, R. N. P., Reynolds, K., Almond, E. J. P., Marston, S. D., Emond, R. T. D. Clin. exp. Immun. 1973, 13, 359. Jones, J. V. in Proceedings of the Third Symposium on Impaired Cell-mediated Hypersensitivity in Man (edited by J. F. Jennings and D. J. Ward); p. 81. Robert Jones and Agnes Hunt Orthopædic Hospital Management Committee, Oswestry, 1970. Diehl, V., Henle, G., Henle, W., Kohn, G. J. Virol. 1968, 2, 663. Marston, S. D., Almond, E. J. P., Bishun, N. P., Maunsell, E. D., Sutton, R. N. P. J. clin. Path. 1972, 25, 701. Achong, B. G. ibid. 1972, 25, suppl. 6, p. 51. Kufe, D., Hehlmann, R., Spiegelman, S. Proc. natn. Acad. Sci. U.S.A. 1973, 70, 5. Huebner, R. J., Kelloff, G. J., Sarma, P. S., Lane, W. T., Turner, H. C. ibid. 1970, 67, 366. Siegel, S. Non-parametric Statistics. New York, 1956.
;
Preliminary
Communications
TUBERCULIN ANERGY AND INFECTIOUS MONONUCLEOSIS S. HAIDER
M. DE L. COUTINHO R. T. D. EMOND
of illness which became positive when they were tested 6 weeks later; five of these eight gave a definite history of B.C.G. vaccination. These results (see table) suggest that in a considerable number of patients (35%) there was a transient depression of cellmediated immunity during the acute phase of infectious mononucleosis:
Royal Free Hospital Infectious Diseases Unit, Coppetts Wood Hospital, London N10 1JN R. N. P. SUTTON
Department of Medical Microbiology, King’s College Hospital Medical School, London SE5 8RX DISCUSSION
Cell-mediated immunity, as assessed Summary by the response to tuberculin, was in investigated twenty-three patients with infectious mononucleosis. In eight patients, negative reactions were observed during acute illness which became positive during convalescence, suggesting that there had been a temporary depression of cell-mediated
immunity. INTRODUCTION
THE recognition that the Epstein-Barr (E.B.) virus is the probable causative agent in infectious mononucleosis 1,2 has led to a resurgence of interest in this disease. Immunologically, the most impressive feature of infectious mononucleosis is the development of a medley of inappropriate " antibodies which are probably, in part at least, responsible for the high levels of immunoglobulins found in this disease.3-5 The humoral limb of the immune response thus remains intact, although functioning somewhat aberrantly. What happens to cell-mediated immunity in the acute phase of infectious mononucleosis is not well documented, apart from one reportof transient depression of the tuberculin response. Tuberculin reactivity is an efferent activity of the T lymphocyte in response to intradermal tuberculin. A positive reaction expresses an intact cell-mediated immunity system in an individual who, in the past, has been exposed to Mycobacterium tuberculosis, and non-reactivity in such a person indicates an abnormality in this system. The conversion from non-reactivity to a reactive state indicates recovery from a transient immunological depression affecting this system. We used this simple test to assess the cell-mediated immunity in infectious mononucleosis. "
The exact mechanism of this transient depression of the cell-mediated immune response is not clear. Is it due to virus multiplication in the T lymphocytes
with consequent functional impairment ? E.B. virus particles are, in vitro, cleared from cultured infectious-mononucleosis leucocytes within 2-3 not but we do know what happens in vivo; months,7,8 can failure of clearance occur and, if so, could it result in continued immunosuppression ? There are further implications of this transient immunological depression in infectious mononucleosis. The association of the herpes-like E.B. virus with infectious mononucleosis, with Burkitt’s lymphoma, and with some types of nasopharyngeal carcinoma is now well recognised.4,9 There have been reports that nucleic acid homologous with that of the R.N.A. Rauscher murine-leukxmia virus has been detected in Burkitt’s tumour and in nasopharyngealThese apparently conflicting carcinoma cells of observations groups may be reconciled if we that of cell-mediated immunity accept depression E.B. virus infection (as in infectious monoby nucleosis) could provide the necessary stimulus to activate an otherwise dormant virus genome.11 The disturbance of cell-mediated immunity in infectious mononucleosis and in the more frequent asymptomatic infections with the E.B. virus deserves further investigation as a possible mechanism for the induction of malignant change in man. We are grateful to Dr Hillas Smith for his permission include some of the patients admitted under his care. Requests for reprints should be addressed to S. H. REFERENCES 1. 2.
PATIENTS AND METHODS
infectious mononucleosis, including heterophile antibodies and typical abnormal white blood-cells, were investigated. All were given an intradermal test of 1/10,000 tuberculin during the acute phase of the illness, and this test was repeated 6 weeks later. The tests were read after 48 hours and an area of induration of 8 mm. or over was considered to be Patients
with
clinical features
of
positive. RESULTS
patients with infectious monoincluded in this survey. Eight gave tuberculin reaction during the acute phase
3. 4. 5. 6.
7. 8. 9. 10.
Twenty-three nucleosis a
negative
were
to
11. 12.
Henle, G., Henle, W., Diehl, V. Proc. natn. Acad. Sci. U.S.A. 1968, 59, 94. Niedermann, J. C., Evans, A. S., Subrahmanyan, L., McCollum, R. W. New Engl. J. Med. 1970, 282, 361. Wollheim, F. A., Williams, R. C. ibid. 1966, 274, 61. Sutton, R. N. P. J. clin. Path. 1972, 25, suppl. 6, p. 58. Sutton, R. N. P., Reynolds, K., Almond, E. J. P., Marston, S. D., Emond, R. T. D. Clin. exp. Immun. 1973, 13, 359. Jones, J. V. in Proceedings of the Third Symposium on Impaired Cell-mediated Hypersensitivity in Man (edited by J. F. Jennings and D. J. Ward); p. 81. Robert Jones and Agnes Hunt Orthopædic Hospital Management Committee, Oswestry, 1970. Diehl, V., Henle, G., Henle, W., Kohn, G. J. Virol. 1968, 2, 663. Marston, S. D., Almond, E. J. P., Bishun, N. P., Maunsell, E. D., Sutton, R. N. P. J. clin. Path. 1972, 25, 701. Achong, B. G. ibid. 1972, 25, suppl. 6, p. 51. Kufe, D., Hehlmann, R., Spiegelman, S. Proc. natn. Acad. Sci. U.S.A. 1973, 70, 5. Huebner, R. J., Kelloff, G. J., Sarma, P. S., Lane, W. T., Turner, H. C. ibid. 1970, 67, 366. Siegel, S. Non-parametric Statistics. New York, 1956.
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