Ricardo U. Sorensen

Newborn lymphocyte subpopulations: The influence of labor

Cord blood mononuclear cell subsets were enumerated in 31 neonates delivered after maternal labor, in 25 neonates delivered by cesarean section without preceding labor, and in 60 healthy adults. In neonates born with and without preceding labor percentages of CD3 cells were lower than those in adults (63% and 60% as opposed to 83% in adults). However, the absolute numbers of CD3 cells were significantly greater in newborn infants delivered without preceding labor (3.287 +/- 1.451 cells per microliter) than in both neonates born after labor (2.660 +/- 800 cells per microliter) and in adults (2.189 +/- 807 cells per microliter). The increase in CD3 cells in infants delivered without preceding labor reflects increased numbers of CD4-positive cells. This increase in the absolute number of T lymphocytes and CD4 (helper) lymphocytes was significant (p less than 0.02). These data indicate that labor-related stress significantly decreases the total number of neonatal T lymphocytes and the CD4 (helper) T-cell subpopulation in cord blood.

Normal lymphocyte responses to mitogens in term and premature neonates following normal and abnormal intrauterine growth

Cord blood lymphocyte responses to a panel of four mitogens were studied in 242 neonates using a whole blood technique. The patient population was divided into five gestational-age groups: 20-27.9, 28-32.9, 33-37.9, 38-41.9, and 42-44 weeks. Neonatal lymphocytes undergo a continuous reduction in proliferative responsiveness to the polyclonal ligands phytohemagglutinin (PHA) and concanavalin A (Con A) as gestation progresses from 20 to 44 weeks postconception. This is consistent with their change in unstimulated in vitro blastogenesis which when measured over the same developmental period is greatest in more immature neonates. Neonatal lymphocyte proliferative responsiveness to pokeweed mitogen (PWM) and staphylococcus protein A (SpA), however, was unrelated to gestational age. The influence of intrauterine nutritional deprivation on lymphocyte proliferative responses was studied in clinically uninfected newborns and compared to gestational age-matched controls with a normal nutritional status. Intrauterine nutritional deprivation was not associated with a decrease in mitogen-induced lymphocyte proliferation. Further, we explored the influence of several perinatal clinical settings commonly associated with fetal distress on cord blood lymphocyte responses to mitogens. Although perinatal stress in the form of low Apgar scores, meconium-stained amniotic fluid, and prolonged rupture of the amniotic membranes was not related to differences in mitogen induced lymphocyte proliferation, mode of delivery was. Cesarean section delivery as compared to vaginal delivery was associated with a significantly greater PHA-, Con A-, and SpA-induced neonatal lymphocyte response. Several alternative explanations for this finding are explored. Lastly, the purified protein thymosin fraction 5 was not associated with alteration in either neonatal or adult mitogen-induced lymphocyte proliferation.

Natural cytotoxicity in immunodeficiency diseases: Preservation of natural killer activity and the in vivo appearance of radioresistant killing

We studied spontaneous natural killer (NK) cell activity and radiation-resistant NK mediated cytotoxicity in four patients with clinically documented severe combined immune deficiency disease (SCID), and in one subject each with intestinal lymphangiectasia and cartilage-hair hypoplasia. We observed the preservation of spontaneous NK activity in all patients despite the presence of profound B- and T-lymphocytopenia and clinical immunodeficiency. NK activity was associated with relatively normal circulating numbers of OKM1+ lymphocytes, a population known to contain NK effectors. Spontaneous NK activity resistant to 3000 rad was increased in all patients, indicating the presence of activated natural killer cells in vivo. The concept of a chronically activated immune system in these patients was further supported by the presence of increased Ia positive T cells in all subjects tested, suggesting that radioresistant NK activity may be a useful parameter to measure when assessing in vivo immune activation. Our data, as well as that of others, supports the hypothesis that at least one population of NK cells is a distinct lineage arising at the differentiation level of myeloid and lymphoid stem cells in the bone marrow.

Lymphocyte responses of human neonates to bacterial antigens

Abstract Antibiotic-killed bacteria have been shown to induce in vitro lymphocyte proliferation in normal adults. To study the development of this reactivity, we analyzed the responses of cord blood lymphocytes to Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae , and to the plant lectins phytohemagglutinin, concanavalin A, and pokeweed mitogen. Cord blood lymphocytes incorporated thymidine in response to plant mitogens and whole antibiotic-killed bacteria at levels similar to those of adult PBL. However, while all neonates responded to plant lectins, one-fifth of neonates did not respond to any of the bacteria studied. In addition, a large group of neonates responded to Staphylococcus but not to pseudomonas or klebsiella. In newborns, there was a significant correlation between responses to pseudomonas and responses to klebsiella but not between responses to Staphylococcus and responses to either gram-negative strain. We suggest that the capability for immune recognition of bacteria is present in most human neonates, but that different developmental processes are required for the proliferative responses to plant mitogens, to antibiotic-killed Staphylococcus, and to the gram-negative bacteria used.

Cell-Mediated Immune Responses to Chlamydia trachomatis in Mothers and Infants

Abstract Cell-mediated immunity to Chlamydia trachomatis was studied in pregnant women with chlamydial infection of the cervix, in infants born vaginally to these women, and in infants presenting with chlamydial conjunctivitis. Uninfected pregnant women and their infants were studied as controls. McCoy cell cultures were used to isolate C. trachomatis from clinical specimens. Cell-mediated immunity was measured by lymphocyte proliferative responses in vitro to stimulation by chlamydial antigens. Chlamydial IgG antibody in serum specimens was detected by a micro-enzyme-linked immunosorbent assay technique. The mean lymphocyte proliferative responses to chlamydial antigens were greater in infected women than in uninfected women both during pregnancy and in the postpartum period. Lymphocyte responsiveness in infected pregnant women, however, was less than in postpartum women. Despite failure to detect chlamydial infection in exposed infants, lymphocyte proliferative responses were greater in umbilical cord blood and later in peripheral blood samples from neonates born to infected mothers than in infants born to uninfected mothers. These responses were also greater in infants with chlamydial conjunctivitis than in infants of uninfected mothers. These data suggest that cellular immune responses to chlamydial antigens are increased in infected mothers and infants and that infants may acquire chlamydial cell-mediated immunity transplacentally.

Lymphocyte proliferation in a 31-week premature neonate with 69, XXX chromosomal constitution*

The clinical syndrome of triploidy has only recently been described with its phenotypic characteristics emerging from a series of descriptive case reports. This paper describes the mitogen induced lymphocyte proliferative responses of a 31‐week gestation neonate. Similar data, collected simultaneously, from 27 healthy 30–32‐week gestation neonates is also reported for comparison. Since the capability of lymphocytes to become activated is dependent on and indicative of the hosts ability to develop a cellular immune reaction, these data indicate no diminution in cell mediated immunity by this polyploid individual.