Abstract
In vitro rubella virus infections of lymphocytes from normal adult humans impaired their responsiveness to phytohemagglutinin (PHA) stimulations; a situation which seemed analogous to the PHA unresponsiveness of peripheral lymphocytes from babies with the congenital rubella syndrome. Such in vitro viral infection of normal cells also decreased the synthesis of normal nucleic acids and structural proteins, and abrogated the enhanced DNA synthesis induced by pokeweed and specific antigen stimulations. Furthermore, it was shown that live rubella virus, but not ultraviolet-irradiated virus, was necessary for the impaired mitogenic responses of normal leukocytes. These observations are interpreted to favor the view that the virus achieves its inhibitory effect on the action of mitogens by interference either directly or indirectly at an intracellular site. Such an action could reduce the functional potential of lymphocytes and impair their effectiveness as immunologically competent cells or as effectors in immunologic reactions.
Full Text
The Full Text of this article is available as a PDF (1.2 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- ALFORD C. A., Jr, NEVA F. A., WELLER T. H. VIROLOGIC AND SEROLOGIC STUDIES ON HUMAN PRODUCTS OF CONCEPTION AFTER MATERNAL RUBELLA. N Engl J Med. 1964 Dec 17;271:1275–1281. doi: 10.1056/NEJM196412172712501. [DOI] [PubMed] [Google Scholar]
- Alford C. A., Jr Studies on antibody in congenital rubella infections. I. Physicochemical and immunologic investigations of rubella neutralizing antibody. Am J Dis Child. 1965 Oct;110(4):455–463. doi: 10.1001/archpedi.1965.02090030475019. [DOI] [PubMed] [Google Scholar]
- Astaldi G., Massimo L., Airo R., Mori P. G. Phytohaemagglutinin and lymphocytes from acute lymphocytic leukaemia. Lancet. 1966 Jun 4;1(7449):1265–1266. doi: 10.1016/s0140-6736(66)90279-0. [DOI] [PubMed] [Google Scholar]
- BACH F., HIRSCHHORN K. GAMMA-GLOBULIN PRODUCTION BY HUMAN LYMPHOCYTES IN VITRO. Exp Cell Res. 1963 Dec;32:592–595. doi: 10.1016/0014-4827(63)90197-6. [DOI] [PubMed] [Google Scholar]
- BECKMAN L. Effect of phytohaemagglutinin on human serum and cell proteins. Nature. 1962 Aug 11;195:582–583. doi: 10.1038/195582a0. [DOI] [PubMed] [Google Scholar]
- BENYESH-MELNICK M., DESSY S. I., FERNBACH D. J. CYTOMEGALOVIRURIA IN CHILDREN WITH ACUTE LEUKEMIA AND IN OTHER CHILDREN. Proc Soc Exp Biol Med. 1964 Nov;117:624–630. doi: 10.3181/00379727-117-29654. [DOI] [PubMed] [Google Scholar]
- Bach F. H., Voynow N. K. One-way stimulation in mixed leukocyte cultures. Science. 1966 Jul 29;153(3735):545–547. doi: 10.1126/science.153.3735.545. [DOI] [PubMed] [Google Scholar]
- Banatvala J. E., Horstmann D. M., Payne M. C., Gluck L. Rubella syndrome and thrombocytopenic purpura in newborn infants. Clinical and virologic observations. N Engl J Med. 1965 Aug 26;273(9):474–478. doi: 10.1056/NEJM196508262730904. [DOI] [PubMed] [Google Scholar]
- Bellanti J. A., Artenstein M. S., Olson L. C., Buescher E. L., Luhrs C. E., Milstead K. L. Congenital rubella. Clinicopathologic, virologic, and immunologic studies. Am J Dis Child. 1965 Oct;110(4):464–472. doi: 10.1001/archpedi.1965.02090030484020. [DOI] [PubMed] [Google Scholar]
- Börjeson J., Reisfeld R., Chessin L. N., Welsh P. D., Douglas S. D. Studies on human peripheral blood lymphocytes in vitro. I. Biological and physicochemical properties of the pokeweed mitogen. J Exp Med. 1966 Nov 1;124(5):859–872. doi: 10.1084/jem.124.5.859. [DOI] [PMC free article] [PubMed] [Google Scholar]
- COULSON A. S., CHALMERS D. G. EFFECTS OF PHYTOHAEMAGGLUTININ ON LEUCOCYTES. Lancet. 1964 Oct 10;2(7363):819–820. doi: 10.1016/s0140-6736(64)90598-7. [DOI] [PubMed] [Google Scholar]
- Chessin L. N., Börjeson J., Welsh P. D., Douglas S. D., Cooper H. L. Studies on human peripheral blood lymphocytes in vitro. II. Morphological and biochemical studies on the transformation of lymphocytes by pokeweed mitogen. J Exp Med. 1966 Nov 1;124(5):873–884. doi: 10.1084/jem.124.5.873. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cooper H. L., Rubin A. D. Synthesis of nonribosomal RNA by lymphocytes: a response to phytohemagglutinin treatment. Science. 1966 Apr 22;152(3721):516–518. doi: 10.1126/science.152.3721.516. [DOI] [PubMed] [Google Scholar]
- Copperman R., Morton H. E. Reversible inhibition of mitosis in lymphocyte cultures by non-viable Mycoplasma. Proc Soc Exp Biol Med. 1966 Dec;123(3):790–795. doi: 10.3181/00379727-123-31605. [DOI] [PubMed] [Google Scholar]
- Dutton R. W. Symposium on in vitro studies of the immune response. II. Significance of the reaction of lymphoid cells to homologous tissue. Bacteriol Rev. 1966 Jun;30(2):397–407. doi: 10.1128/br.30.2.397-407.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
- GUDE W. D., UPTON A. C., ODELL T. T., Jr Giemsa staining of autoradiograms prepared with stripping film. Stain Technol. 1955 Jul;30(4):161–162. doi: 10.3109/10520295509114458. [DOI] [PubMed] [Google Scholar]
- HIRSCHHORN K., SCHREIBMAN R. R., BACH F. H., SILTZBACH L. E. IN-VITRO STUDIES OF LYMPHOCYTES FROM PATIENTS WITH SARCOIDOSIS AND LYMPHOPROLIFERATIVE DISEASES. Lancet. 1964 Oct 17;2(7364):842–843. doi: 10.1016/s0140-6736(64)90691-9. [DOI] [PubMed] [Google Scholar]
- Hersh E. M., Oppenheim J. J. Impaired in vitro lymphocyte transformation in Hodgkin's disease. N Engl J Med. 1965 Nov 4;273(19):1006–1012. doi: 10.1056/NEJM196511042731903. [DOI] [PubMed] [Google Scholar]
- Kleinsmith L. J., Allfrey V. G., Mirsky A. E. Phosphorylation of nuclear protein early in the course of gene activation in lymphocytes. Science. 1966 Nov 11;154(3750):780–781. doi: 10.1126/science.154.3750.780. [DOI] [PubMed] [Google Scholar]
- LING N. R., HUSBAND E. M. SPECIFIC AND NON-SPECIFIC STIMULATION OF PERIPHERAL LYMPHOCYTES. Lancet. 1964 Feb 15;1(7329):363–365. doi: 10.1016/s0140-6736(64)92102-6. [DOI] [PubMed] [Google Scholar]
- Leikin S. L., Bazelon M., Park K. H. In vitro lymphocyte transformation in ataxia telangiectasia. J Pediatr. 1966 Mar;68(3):477–479. doi: 10.1016/s0022-3476(66)80255-x. [DOI] [PubMed] [Google Scholar]
- Lindquist J. M., Plotkin S. A., Shaw L., Gilden R. V., Williams M. L. Congenital rubella syndrome as a systemic infection. Studies of affected infants born in Philadelphia, U.S.A. Br Med J. 1965 Dec 11;2(5475):1401–1406. doi: 10.1136/bmj.2.5475.1401. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maassab H. F., Veronelli J. A. Characteristics of serially propagated monkey kidney cell cultures with persistent rubella infection. J Bacteriol. 1966 Jan;91(1):436–441. doi: 10.1128/jb.91.1.436-441.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McClain M. E., Spendlove R. S. Multiplicity reactivation of reovirus particles after exposure to ultraviolet light. J Bacteriol. 1966 Nov;92(5):1422–1429. doi: 10.1128/jb.92.5.1422-1429.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mella B., Lang D. J. Leukocyte mitosis: suppression in vitro associated with acute infectious hepatitis. Science. 1967 Jan 6;155(3758):80–81. doi: 10.1126/science.155.3758.80. [DOI] [PubMed] [Google Scholar]
- Meuwissen H. J., Good R. A. Suppression of graft versus host reaction by Mitomycin C. Nature. 1967 Aug 5;215(5101):634–635. doi: 10.1038/215634a0. [DOI] [PubMed] [Google Scholar]
- Montgomery J. R., South M. A., Rawls W. E., Melnick J. L., Olson G. B., Dent P. B., Good R. A. Viral inhibition of lymphocyte response to phytohemagglutinin. Science. 1967 Sep 1;157(3792):1068–1070. doi: 10.1126/science.157.3792.1068. [DOI] [PubMed] [Google Scholar]
- NOWELL P. C. Phytohemagglutinin: an initiator of mitosis in cultures of normal human leukocytes. Cancer Res. 1960 May;20:462–466. [PubMed] [Google Scholar]
- OPPENHEIM J. J., WHANG J., FREI E., 3rd IMMUNOLOGIC AND CYTOGENETIC STUDIES OF CHRONIC LYMPHOCYTIC LEUKEMIC CELLS. Blood. 1965 Aug;26:121–132. [PubMed] [Google Scholar]
- Old L. J., Boyse E. A. Antigens of tumors and leukemias induced by viruses. Fed Proc. 1965 Sep-Oct;24(5):1009–1017. [PubMed] [Google Scholar]
- Olson G. B., South M. A., Good R. A. Phytohaemagglutinin unresponsiveness of lymphocytes from babies with congenital rubella. Nature. 1967 May 13;214(5089):695–696. doi: 10.1038/214695a0. [DOI] [PubMed] [Google Scholar]
- Pappenheimer A. M. EXPERIMENTAL STUDIES UPON LYMPHOCYTES : I. THE REACTIONS OF LYMPHOCYTES UNDER VARIOUS EXPERIMENTAL CONDITIONS. J Exp Med. 1917 May 1;25(5):633–650. doi: 10.1084/jem.25.5.633. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Parenti F., Franceschini P., Forti G., Cepellini R. The effect of phytohaemagglutinin on the metabolism and gamma-globulin synthesis of human lymphocytes. Biochim Biophys Acta. 1966 Jul 20;123(1):181–187. doi: 10.1016/0005-2787(66)90171-7. [DOI] [PubMed] [Google Scholar]
- Plotkin S. A., Klaus R. M., Whitely J. P. Hypogammaglobulinemia in an infant with congenital rubella syndrome; failure of 1-adamantanamine to stop irus excretion. J Pediatr. 1966 Dec;69(6):1085–1091. doi: 10.1016/s0022-3476(66)80299-8. [DOI] [PubMed] [Google Scholar]
- RIGAS D. A., JOHNSON E. A. STUDIES ON THE PHYTOHEMAGGLUTININ OF PHASEOLUS VULGARIS AND ITS MITOGENICITY. Ann N Y Acad Sci. 1964 Feb 28;113:800–818. doi: 10.1111/j.1749-6632.1964.tb40705.x. [DOI] [PubMed] [Google Scholar]
- RUBIN H., FANSHIER L., CORNELIUS A., HUGHES W. F. Tolerance and immunity in chickens after congenital and contact infection with an avian leukosis virus. Virology. 1962 May;17:143–156. doi: 10.1016/0042-6822(62)90091-0. [DOI] [PubMed] [Google Scholar]
- RUDOLPH A. J., YOW M. D., PHILLIPS A., DESMOND M. M., BLATTNER R. J., MELNICK J. L. TRANSPLACENTAL RUBELLA INFECTION IN NEWLY BORN INFANTS. JAMA. 1965 Mar 8;191:843–845. doi: 10.1001/jama.1965.03080100061013. [DOI] [PubMed] [Google Scholar]
- Rawls W. E., Melnick J. L., Olson G. B., Dent P. B., Good R. A. Effect of amantadine hydrochloride on the response of human lymphocytes to phytohemagglutinin. Science. 1967 Oct 27;158(3800):506–507. doi: 10.1126/science.158.3800.506. [DOI] [PubMed] [Google Scholar]
- Rawls W. E., Phillips A., Melnick J. L., Desmond M. M. Persistent virus infection in congenital rubella. Arch Ophthalmol. 1967 Apr;77(4):430–433. doi: 10.1001/archopht.1967.00980020432003. [DOI] [PubMed] [Google Scholar]
- Riddle P. R., Berenbaum M. C. Postoperative depression of the lymphocyte response to phytohaemagglutinin. Lancet. 1967 Apr 8;1(7493):746–748. doi: 10.1016/s0140-6736(67)91364-5. [DOI] [PubMed] [Google Scholar]
- Rubin A. D. Lymphocyte RNA synthesis in infectious mononucleosis: the response to phyohemagglutinin in vitro. Blood. 1966 Oct;28(4):602–605. [PubMed] [Google Scholar]
- Sell S., Rowe D. S., Gell P. G. Studies on rabbit lymphocytes in vitro. 3. Proteins, RNA, and DNA synthesis by lymphocyte cultures after stimulation with phytohaemagglutinin, with staphylococcal filtrate, with antiallotype serum, and with heterologous antiserum to rabbit whole serum. J Exp Med. 1965 Oct 1;122(4):823–839. doi: 10.1084/jem.122.4.823. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Soothill J. F., Hayes K., Dudgeon J. A. The immunoglobulins in congenital rubella. Lancet. 1966 Jun 25;1(7452):1385–1388. doi: 10.1016/s0140-6736(66)90299-6. [DOI] [PubMed] [Google Scholar]
- Stewart G. L., Parkman P. D., Hopps H. E., Douglas R. D., Hamilton J. P., Meyer H. M., Jr Rubella-virus hemagglutination-inhibition test. N Engl J Med. 1967 Mar 9;276(10):554–557. doi: 10.1056/NEJM196703092761006. [DOI] [PubMed] [Google Scholar]
- Tormey D. C., Mueller G. C. An assay for the mitogenic activity of phytohemagglutinin preparations. Blood. 1965 Nov;26(5):569–578. [PubMed] [Google Scholar]
- VOLKERT M., LARSEN J. H. STUDIES ON IMMUNOLOGICAL TOLERANCE TO LCM VIRUS. 5. THE INDUCTION OF TOLERANCE TO THE VIRUS. Acta Pathol Microbiol Scand. 1965;63:161–171. doi: 10.1111/apm.1965.63.2.161. [DOI] [PubMed] [Google Scholar]
- Yam L. T., Castoldi G. L., Mitus W. J. Quantitative evaluation of phytohemagglutinin-stimulated lymphocyte cultures. J Lab Clin Med. 1967 Oct;70(4):699–706. [PubMed] [Google Scholar]