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Rosette-forming lymphocytes and measles vaccination
74
Brief cfinical and laboratory observations
meningitis 1-7 and pneumococcal pneumonia in adults. 8-1~ There has been no published study evaluating the potential usefulness of CIE in the diagnosis of pneumococcal pneumonia during childhood, although Shackleford and associates~ demonstrated pneumococcal polysaccharide in sera from all three children with pneumococcal pneumonia whom they tested. The chief emphasis in publications to date has been on the potential of CIE to provide the etiology of the infection before culture results are known. Coonrod and RyteP ~ have shown that adults with severe pneumococcal pneumonia are more apt to be positive by CIE than those with milder disease, and that bacteremia could be demonstrated in only half of those for whom pneumococcal polysaccharides could be detected in concentrated urine by CIE. The present study of pneumonia in children has confirmed the experience in adults, suggesting that CIE can be useful in the diagnosis o f pneumococcal pneumonia when cultures are negative and that this technique will be most helpful in severe pneumococcal pneumonia when pleural effusion or pneumatoceles are present.
REFERENCES 1. Greenwood BM, Whittle HC, and Dominic-Rajkovic O: Countercurrent immunoelectrophoresis in the diagnosis of meningococcal infections, Lancet 2:519, 1971.
Rosette-forming lymphocytes and measles vaccination C. Mandalenaki-Asfi, P. Liakopoulou, M. Apostolou, Th. Thomaidis, and N. Matsaniotis, Athens, Greece MEASLES INFECTION in man may result in depression of cellular immunity. We studied the influence o f attenuated live measles virus on spontaneous rosette formation, a marker of T lymphocytes in peripheral blood. STUDIED
CASES
Seventeen healthy infants, 12 to 18 months of age, who had never had measles infection nor had been vaccinated previously against measles, were immunized with the Edmonston-B attenuated live measles virus. None of them had been exposed recently to the disease. Blood was obtained prior to vaccination and on the ninth, fifteenth,
The Journal of Pediatrics January 1976 2. Hoffman T, and Edwards EA: Group-specific polysaccharide antigen and humoral antibody response in disease due to Neisseria meningitidis, J Infect Dis 126:636, 1972. 3. Coonrod JD, and Rytel MW: Determination of etiology of bacterial meningitis by counterimmunoelectrophoresis, Lancet 1:1154, 1972. 4. Edwards EA, Muehl PM, and Peckinpaugh RO: Diagnosis of bacterial meningitis by counterimmunoelectrophoresis, J Lab (;fin Med 80:449, 1972. 5. Ingrain DL, Anderson P, and Smith DH: Countercurrent immunoelectrophoresis in the diagnosis of systemic diseases caused by Hemophilus influenzae, type B, J PI~DIATR 81:1156, 1972. 6. Fossieck B Jr, Craig R, and Paterson PY: Counterimmunoelectrophoresis for rapid diagnosis of meningitis due to Diplococcus pneumoniae, J Infect Dis 127:106, 1973. 7. Shackelford PG, Campbell J, and Feigen RD: Countercurrent immunoelectrophoresis in the evaluation of childhood infections, J PEDIATR85:478, 1974. 8. Dorff GF, Coonrod JD, and Rytel MW: Detection by immunoelectrophoresis of antigen in sera of patients with pneumococcal bacteremia, Lancet 1:578, 1971. 9. Kenny GE, Wentworth BB, Beasley RP, et al: Correlation of circulating capsular polysaccharide with bacteremia in pneumococcal pneumonia, Infect Immunol 6:431, 1972. 10. Coonrod JD, and Rytel MW: Detection of type-specific pneumocOccal antigens by counterimmunoelectrophoresis. II. Etiologic diagnosis of pneumococcal pneumonia, J Lab Clin Med 81:778, 1973.
and thirty-fifth postvaccination days, respectively, for white blood cell and absolute differential counts and for T-cell quantitative determination. Abbreviation used E: spontaneous rosette formation RESULTS A marked reduction of E rosettes in each infant on the ninth and fifteenth postimmunization days was noted. Prior to immunization the mean value of E rosettes was 1,303/mm ~ of peripheral blood, whereas on day 9 it declined to 270. The difference is statistically* highly significant (t = 9.6, p < 0.001). Furthermore, the marked reduction of E rosettes persisted to the fifteenth day (440/ mm:')~ On the thirty-fifth postimmunization day E rosettes had returned to normal values. Leukocytes also decreased on the ninth postimmunization day (mean value prior to vaccination, 11,580/mm:~; ninth day, 9,980/mm :~ t = 2.4, p < 0.05); the absolute numbers of polymorphonuclear cells and small lympho*Results were statisticallyanalyzedby the paired t-test.
Volume 88 Number 1
Brief clinical and laboratory observations
75
1 soc
E I~
14oc
2 0 L
0
120C
100C
I.. .0
E
eOC
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o
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400
immMfllisti~fl d
o
y
s
Fig. 1. Graphic representation of rosette formation in each case prior to immunization and until the thirty-fifth postimmunization day. cytes decreased proportionately (t = 3.28, p < 0.01 and t = 2.81, p < 0.01, respectively). On days 15 and 35 respectively, there was no statistically significant difference. On the other hand the numbers of large lymphocytes showed a striking increase on the ninth day (mean value prior to vaccination 430/mm:~; day 9, 1,640/mm 3) t = 57.9, p < 0.001) and fifteenth day (mean value, 1,580/mm :', t = 52.6, p < 0.001) as compared, to that immediately before immunization. The increase was still evident on the thirty-fifth day (mean value, 1,200/mm 3, t = 6.18, p < 0.001).
an unlikely cause of such a substantial and persistent decrease of T cells for as long as 15 days after vaccination. A persistent increase in numbers of large lymphocytes was also noted. Whether this p h e n o m e n o n bears any relationship to the reported formation of multinucleated giant cells in some phytohemagglutinin-stimulated cultures of lymphocytes obtained from measles patients cannot be ascertained? In conclusion, reduction in n u m b e r s of E rosettes appears to be intimately related to the administration of live attenuated measles vaccine.
COMMENT Our results indicate a transient but definite decrease of thymus-dependent lymphocytes (T cells) for a period of 15 days after live attenuated measles vaccination. There was also a decrease in numbers of white blood cells, owing to a decrease of both polymorphonuclears and lymphocytes, as usually observed during the course of natural measles infection. Wybron and Fudenberg ~ showed a significant reduction of E rosettes in subjects suffering from various viral infections. The mechanism of this reduction is not known. It might be a direct effect of virus on the cells of the lymphoreticular system in which there is virus replication, thus affecting T cells and on the other h a n d promoting production of large lymphocytes. Lymphocyte trapping 3'* might have played a role in the lymphopenia, but this is
REFERENCES
1. Wybron J, Carr MC, and Fudenberg AH: The human rosette forming cells as a marker of a population of thymus derived cells, J Clin Invest 51:2537, 1972. 2. Wybron J, and Fudenberg HH: Thymus derived rosette forming ceils in various human disease states: Cancer, lymphoma, bacterial and viral infections and other diseases, J Clin Invest 52:1026, 1973. 3. Emeson EE, and Thursh DR: Antigen-induced trapping of immunospecific lymphocytes in the spleen, J Immunol 113:1575, 1974. 4. Zatz MM, and Gershon RK: Thymus dependence of lymphocyte trapping, J Immunol 112:101, 1974. 5. Osunkoya BO, Oyediran, ABO, and Cooke A: Multinucleated giant cells in PHA-stimulated leucocyte cultures of children with measles, Immunology 25:737, 1973.
Brief cfinical and laboratory observations
meningitis 1-7 and pneumococcal pneumonia in adults. 8-1~ There has been no published study evaluating the potential usefulness of CIE in the diagnosis of pneumococcal pneumonia during childhood, although Shackleford and associates~ demonstrated pneumococcal polysaccharide in sera from all three children with pneumococcal pneumonia whom they tested. The chief emphasis in publications to date has been on the potential of CIE to provide the etiology of the infection before culture results are known. Coonrod and RyteP ~ have shown that adults with severe pneumococcal pneumonia are more apt to be positive by CIE than those with milder disease, and that bacteremia could be demonstrated in only half of those for whom pneumococcal polysaccharides could be detected in concentrated urine by CIE. The present study of pneumonia in children has confirmed the experience in adults, suggesting that CIE can be useful in the diagnosis o f pneumococcal pneumonia when cultures are negative and that this technique will be most helpful in severe pneumococcal pneumonia when pleural effusion or pneumatoceles are present.
REFERENCES 1. Greenwood BM, Whittle HC, and Dominic-Rajkovic O: Countercurrent immunoelectrophoresis in the diagnosis of meningococcal infections, Lancet 2:519, 1971.
Rosette-forming lymphocytes and measles vaccination C. Mandalenaki-Asfi, P. Liakopoulou, M. Apostolou, Th. Thomaidis, and N. Matsaniotis, Athens, Greece MEASLES INFECTION in man may result in depression of cellular immunity. We studied the influence o f attenuated live measles virus on spontaneous rosette formation, a marker of T lymphocytes in peripheral blood. STUDIED
CASES
Seventeen healthy infants, 12 to 18 months of age, who had never had measles infection nor had been vaccinated previously against measles, were immunized with the Edmonston-B attenuated live measles virus. None of them had been exposed recently to the disease. Blood was obtained prior to vaccination and on the ninth, fifteenth,
The Journal of Pediatrics January 1976 2. Hoffman T, and Edwards EA: Group-specific polysaccharide antigen and humoral antibody response in disease due to Neisseria meningitidis, J Infect Dis 126:636, 1972. 3. Coonrod JD, and Rytel MW: Determination of etiology of bacterial meningitis by counterimmunoelectrophoresis, Lancet 1:1154, 1972. 4. Edwards EA, Muehl PM, and Peckinpaugh RO: Diagnosis of bacterial meningitis by counterimmunoelectrophoresis, J Lab (;fin Med 80:449, 1972. 5. Ingrain DL, Anderson P, and Smith DH: Countercurrent immunoelectrophoresis in the diagnosis of systemic diseases caused by Hemophilus influenzae, type B, J PI~DIATR 81:1156, 1972. 6. Fossieck B Jr, Craig R, and Paterson PY: Counterimmunoelectrophoresis for rapid diagnosis of meningitis due to Diplococcus pneumoniae, J Infect Dis 127:106, 1973. 7. Shackelford PG, Campbell J, and Feigen RD: Countercurrent immunoelectrophoresis in the evaluation of childhood infections, J PEDIATR85:478, 1974. 8. Dorff GF, Coonrod JD, and Rytel MW: Detection by immunoelectrophoresis of antigen in sera of patients with pneumococcal bacteremia, Lancet 1:578, 1971. 9. Kenny GE, Wentworth BB, Beasley RP, et al: Correlation of circulating capsular polysaccharide with bacteremia in pneumococcal pneumonia, Infect Immunol 6:431, 1972. 10. Coonrod JD, and Rytel MW: Detection of type-specific pneumocOccal antigens by counterimmunoelectrophoresis. II. Etiologic diagnosis of pneumococcal pneumonia, J Lab Clin Med 81:778, 1973.
and thirty-fifth postvaccination days, respectively, for white blood cell and absolute differential counts and for T-cell quantitative determination. Abbreviation used E: spontaneous rosette formation RESULTS A marked reduction of E rosettes in each infant on the ninth and fifteenth postimmunization days was noted. Prior to immunization the mean value of E rosettes was 1,303/mm ~ of peripheral blood, whereas on day 9 it declined to 270. The difference is statistically* highly significant (t = 9.6, p < 0.001). Furthermore, the marked reduction of E rosettes persisted to the fifteenth day (440/ mm:')~ On the thirty-fifth postimmunization day E rosettes had returned to normal values. Leukocytes also decreased on the ninth postimmunization day (mean value prior to vaccination, 11,580/mm:~; ninth day, 9,980/mm :~ t = 2.4, p < 0.05); the absolute numbers of polymorphonuclear cells and small lympho*Results were statisticallyanalyzedby the paired t-test.
Volume 88 Number 1
Brief clinical and laboratory observations
75
1 soc
E I~
14oc
2 0 L
0
120C
100C
I.. .0
E
eOC
c soo
o
I..-
400
immMfllisti~fl d
o
y
s
Fig. 1. Graphic representation of rosette formation in each case prior to immunization and until the thirty-fifth postimmunization day. cytes decreased proportionately (t = 3.28, p < 0.01 and t = 2.81, p < 0.01, respectively). On days 15 and 35 respectively, there was no statistically significant difference. On the other hand the numbers of large lymphocytes showed a striking increase on the ninth day (mean value prior to vaccination 430/mm:~; day 9, 1,640/mm 3) t = 57.9, p < 0.001) and fifteenth day (mean value, 1,580/mm :', t = 52.6, p < 0.001) as compared, to that immediately before immunization. The increase was still evident on the thirty-fifth day (mean value, 1,200/mm 3, t = 6.18, p < 0.001).
an unlikely cause of such a substantial and persistent decrease of T cells for as long as 15 days after vaccination. A persistent increase in numbers of large lymphocytes was also noted. Whether this p h e n o m e n o n bears any relationship to the reported formation of multinucleated giant cells in some phytohemagglutinin-stimulated cultures of lymphocytes obtained from measles patients cannot be ascertained? In conclusion, reduction in n u m b e r s of E rosettes appears to be intimately related to the administration of live attenuated measles vaccine.
COMMENT Our results indicate a transient but definite decrease of thymus-dependent lymphocytes (T cells) for a period of 15 days after live attenuated measles vaccination. There was also a decrease in numbers of white blood cells, owing to a decrease of both polymorphonuclears and lymphocytes, as usually observed during the course of natural measles infection. Wybron and Fudenberg ~ showed a significant reduction of E rosettes in subjects suffering from various viral infections. The mechanism of this reduction is not known. It might be a direct effect of virus on the cells of the lymphoreticular system in which there is virus replication, thus affecting T cells and on the other h a n d promoting production of large lymphocytes. Lymphocyte trapping 3'* might have played a role in the lymphopenia, but this is
REFERENCES
1. Wybron J, Carr MC, and Fudenberg AH: The human rosette forming cells as a marker of a population of thymus derived cells, J Clin Invest 51:2537, 1972. 2. Wybron J, and Fudenberg HH: Thymus derived rosette forming ceils in various human disease states: Cancer, lymphoma, bacterial and viral infections and other diseases, J Clin Invest 52:1026, 1973. 3. Emeson EE, and Thursh DR: Antigen-induced trapping of immunospecific lymphocytes in the spleen, J Immunol 113:1575, 1974. 4. Zatz MM, and Gershon RK: Thymus dependence of lymphocyte trapping, J Immunol 112:101, 1974. 5. Osunkoya BO, Oyediran, ABO, and Cooke A: Multinucleated giant cells in PHA-stimulated leucocyte cultures of children with measles, Immunology 25:737, 1973.