Abstract
Mice from either naive or immunized dams were given intranasal inoculations of Pneumocystis carinii as neonates (24 to 48 h old). Lung P. carinii burdens increased through day 13 postinoculation in all pups and declined to nearly undetectable numbers by day 23 in pups from immune mothers. However, P. carinii numbers in pups from naive mothers did not begin to decline significantly until after day 33, and P. carinii organisms were still detectable in low numbers through day 45. In contrast, the lungs of naive or immunized adult mice contained detectable numbers of P. carinii organisms only up to 9 or 3 days, respectively, after inoculation. The onset of clearance of P. carinii organisms from the lungs of neonatal mice and naive adults was coincident with infiltration of neutrophils and CD4+ CD45RBlo cells into the alveolar spaces and increased titers of P. carinii-specific antibody in sera. Immunized dams had high levels of P. carinii-specific antibody in both their sera and milk, and pups from these dams had higher titers of P. carinii-specific antibody than did pups from naive dams. These data indicate that P. carinii survives for a much longer period in neonates than in adult mice, which is the result of a delay in the onset of the immune response in neonates. Furthermore, immunized mothers contributed to an early clearance of P. carinii organisms by their offspring presumably because of the transfer of P. carinii-specific antibody. However, the passively acquired antibody did not seem to have an effect until the neonates began to mount their own responses.
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- Adkins B., Ghanei A., Hamilton K. Up-regulation of murine neonatal T helper cell responses by accessory cell factors. J Immunol. 1994 Oct 15;153(8):3378–3385. [PubMed] [Google Scholar]
- Adkins B., Hamilton K. Freshly isolated, murine neonatal T cells produce IL-4 in response to anti-CD3 stimulation. J Immunol. 1992 Dec 1;149(11):3448–3455. [PubMed] [Google Scholar]
- Brugnoni D., Airò P., Graf D., Marconi M., Lebowitz M., Plebani A., Giliani S., Malacarne F., Cattaneo R., Ugazio A. G. Ineffective expression of CD40 ligand on cord blood T cells may contribute to poor immunoglobulin production in the newborn. Eur J Immunol. 1994 Aug;24(8):1919–1924. doi: 10.1002/eji.1830240831. [DOI] [PubMed] [Google Scholar]
- Burgio G. R., Ugazio A. G., Notarangelo L. D. Immunology of the neonate. Curr Opin Immunol. 1989;2(5):770–777. doi: 10.1016/0952-7915(90)90049-m. [DOI] [PubMed] [Google Scholar]
- Chen W., Havell E. A., Gigliotti F., Harmsen A. G. Interleukin-6 production in a murine model of Pneumocystis carinii pneumonia: relation to resistance and inflammatory response. Infect Immun. 1993 Jan;61(1):97–102. doi: 10.1128/iai.61.1.97-102.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen W., Havell E. A., Harmsen A. G. Importance of endogenous tumor necrosis factor alpha and gamma interferon in host resistance against Pneumocystis carinii infection. Infect Immun. 1992 Apr;60(4):1279–1284. doi: 10.1128/iai.60.4.1279-1284.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Coutinho G. C., Delassus S., Kourilsky P., Bandeira A., Coutinho A. Developmental shift in the patterns of interleukin production in early post-natal life. Eur J Immunol. 1994 Aug;24(8):1858–1862. doi: 10.1002/eji.1830240821. [DOI] [PubMed] [Google Scholar]
- Cushion M. T., Ruffolo J. J., Walzer P. D. Analysis of the developmental stages of Pneumocystis carinii, in vitro. Lab Invest. 1988 Mar;58(3):324–331. [PubMed] [Google Scholar]
- Demeure C. E., Wu C. Y., Shu U., Schneider P. V., Heusser C., Yssel H., Delespesse G. In vitro maturation of human neonatal CD4 T lymphocytes. II. Cytokines present at priming modulate the development of lymphokine production. J Immunol. 1994 May 15;152(10):4775–4782. [PubMed] [Google Scholar]
- Durandy A., De Saint Basile G., Lisowska-Grospierre B., Gauchat J. F., Forveille M., Kroczek R. A., Bonnefoy J. Y., Fischer A. Undetectable CD40 ligand expression on T cells and low B cell responses to CD40 binding agonists in human newborns. J Immunol. 1995 Feb 15;154(4):1560–1568. [PubMed] [Google Scholar]
- Englund J. A., Mbawuike I. N., Hammill H., Holleman M. C., Baxter B. D., Glezen W. P. Maternal immunization with influenza or tetanus toxoid vaccine for passive antibody protection in young infants. J Infect Dis. 1993 Sep;168(3):647–656. doi: 10.1093/infdis/168.3.647. [DOI] [PubMed] [Google Scholar]
- Fuleihan R., Ahern D., Geha R. S. Decreased expression of the ligand for CD40 in newborn lymphocytes. Eur J Immunol. 1994 Aug;24(8):1925–1928. doi: 10.1002/eji.1830240832. [DOI] [PubMed] [Google Scholar]
- Harmsen A. G., Chen W., Gigliotti F. Active immunity to Pneumocystis carinii reinfection in T-cell-depleted mice. Infect Immun. 1995 Jul;63(7):2391–2395. doi: 10.1128/iai.63.7.2391-2395.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harmsen A. G., Stankiewicz M. Requirement for CD4+ cells in resistance to Pneumocystis carinii pneumonia in mice. J Exp Med. 1990 Sep 1;172(3):937–945. doi: 10.1084/jem.172.3.937. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee C. J., Ching E. D., Vickers J. H. Maternal immunity and antibody response of neonatal mice to pneumococcal type 19F polysaccharide. J Clin Microbiol. 1991 Sep;29(9):1904–1909. doi: 10.1128/jcm.29.9.1904-1909.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee C. J., Wang T. R. Pneumococcal infection and immunization in children. Crit Rev Microbiol. 1994;20(1):1–12. doi: 10.3109/10408419409113544. [DOI] [PubMed] [Google Scholar]
- Lee W. T., Yin X. M., Vitetta E. S. Functional and ontogenetic analysis of murine CD45Rhi and CD45Rlo CD4+ T cells. J Immunol. 1990 May 1;144(9):3288–3295. [PubMed] [Google Scholar]
- Mbawuike I. N., Six H. R., Cate T. R., Couch R. B. Vaccination with inactivated influenza A virus during pregnancy protects neonatal mice against lethal challenge by influenza A viruses representing three subtypes. J Virol. 1990 Mar;64(3):1370–1374. doi: 10.1128/jvi.64.3.1370-1374.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nonoyama S., Penix L. A., Edwards C. P., Lewis D. B., Ito S., Aruffo A., Wilson C. B., Ochs H. D. Diminished expression of CD40 ligand by activated neonatal T cells. J Clin Invest. 1995 Jan;95(1):66–75. doi: 10.1172/JCI117677. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Peglow S. L., Smulian A. G., Linke M. J., Pogue C. L., Nurre S., Crisler J., Phair J., Gold J. W., Armstrong D., Walzer P. D. Serologic responses to Pneumocystis carinii antigens in health and disease. J Infect Dis. 1990 Feb;161(2):296–306. doi: 10.1093/infdis/161.2.296. [DOI] [PubMed] [Google Scholar]
- Rogers M. F., Thomas P. A., Starcher E. T., Noa M. C., Bush T. J., Jaffe H. W. Acquired immunodeficiency syndrome in children: report of the Centers for Disease Control National Surveillance, 1982 to 1985. Pediatrics. 1987 Jun;79(6):1008–1014. [PubMed] [Google Scholar]
- Roths J. B., Sidman C. L. Both immunity and hyperresponsiveness to Pneumocystis carinii result from transfer of CD4+ but not CD8+ T cells into severe combined immunodeficiency mice. J Clin Invest. 1992 Aug;90(2):673–678. doi: 10.1172/JCI115910. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schibler K. R., Liechty K. W., White W. L., Rothstein G., Christensen R. D. Defective production of interleukin-6 by monocytes: a possible mechanism underlying several host defense deficiencies of neonates. Pediatr Res. 1992 Jan;31(1):18–21. doi: 10.1203/00006450-199201000-00003. [DOI] [PubMed] [Google Scholar]
- Schnorr K. L., Pearson L. D. Intestinal absorption of maternal leucocytes by newborn lambs. J Reprod Immunol. 1984 Aug;6(5):329–337. doi: 10.1016/0165-0378(84)90031-7. [DOI] [PubMed] [Google Scholar]
- Shellito J., Suzara V. V., Blumenfeld W., Beck J. M., Steger H. J., Ermak T. H. A new model of Pneumocystis carinii infection in mice selectively depleted of helper T lymphocytes. J Clin Invest. 1990 May;85(5):1686–1693. doi: 10.1172/JCI114621. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Soulez B., Dei-Cas E., Charet P., Mougeot G., Caillaux M., Camus D. The young rabbit: a nonimmunosuppressed model for Pneumocystis carinii pneumonia. J Infect Dis. 1989 Aug;160(2):355–356. doi: 10.1093/infdis/160.2.355. [DOI] [PubMed] [Google Scholar]
- Su T. H., Martin W. J., 2nd Pathogenesis and host response in Pneumocystis carinii pneumonia. Annu Rev Med. 1994;45:261–272. doi: 10.1146/annurev.med.45.1.261. [DOI] [PubMed] [Google Scholar]
- Tsuji T., Nibu R., Iwai K., Kanegane H., Yachie A., Seki H., Miyawaki T., Taniguchi N. Efficient induction of immunoglobulin production in neonatal naive B cells by memory CD4+ T cell subset expressing homing receptor L-selectin. J Immunol. 1994 May 1;152(9):4417–4424. [PubMed] [Google Scholar]
- Wiley J. A., Harmsen A. G. CD40 ligand is required for resolution of Pneumocystis carinii pneumonia in mice. J Immunol. 1995 Oct 1;155(7):3525–3529. [PubMed] [Google Scholar]
- Wilson C. B., Lewis D. B. Basis and implications of selectively diminished cytokine production in neonatal susceptibility to infection. Rev Infect Dis. 1990 May-Jun;12 (Suppl 4):S410–S420. doi: 10.1093/clinids/12.supplement_4.s410. [DOI] [PubMed] [Google Scholar]