Response of Human Newborn Lymphocytes to Alloantigen: Lack of Evidence for Suppression Induction

Hayward, Anthony R.; Malmberg, Susan

doi:10.1203/00006450-198405000-00004

Cited by 11 publications

(5 citation statements)

References 7 publications

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“…After birth the newborn infant's response to foreign lymphocytes can be studied in more detail. Our own studies suggest that blood transfusion in the newborn infant elicits a response by T8+ lymphocytes and that, in tissue culture, there is little difference between the newborn and adult response to foreign histocompatibility antigens (Hayward and Law, 1984).…”

Section: Immunity Development: Clinical Correlatesmentioning

confidence: 80%

“…The response of newborn T cells to alloantigen is very similar to that of adult T cells as regards both the frequency of responders and their phenotype (Hayward and Law, 1984). Evidence that alloantigen responses in newborn infants are mature also comes from the finding that skin grafts applied to them are subsequently rejected (Fowler et aI., 1960).…”

Section: T-cell Mbturity At Birthmentioning

confidence: 96%

See 1 more Smart Citation

Human Growth

1986

106

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Section: Immunity Development: Clinical Correlatesmentioning

confidence: 80%

Section: T-cell Mbturity At Birthmentioning

confidence: 96%

Human Growth

1986

106

View full text Add to dashboard Cite

“…Others have demonstrated that newborn T cells incubated with either adult or neonatal B cells significantly inhibit B cell differentiation and immunoglobulin synthesis (14)(15)(16). These suppressive effccts are also abolished by irradiation, suggesting the need for ongoing cell division for suppression to occur.…”

Section: Resultsmentioning

confidence: 99%

“…(1 3) showed that Con A-activated newborn cells have suppressive activity, but it was significantly less than that of Con A-activated cells from older children. Recently Hayward and Malmberg ( 14) reported that the higher frequency of dividing newborn cells in a 2-way newborn-adult MLC was due to increased proliferation by newborn non-T cells rather than newborn suppression of the adult T cells (10). This increased proliferation could be eliminated by irradiating the non-T cells.…”

Section: Resultsmentioning

confidence: 99%

Lack of Suppression by Concanavalin A-Activated Neonatal Mononuclear Cells

1985

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ABSTRACT. We studied the mixed leukocyte culture suppression generated by cord and newborn mononuclear cells stimulated by concanavalin A (Con A) compared to normal adult cells and cells from patients with systemic lupus erythematosus. Also we studied the effect of supernatants from cord or adult cells stimulated with Con A linked to sepharose (Con A sepharose). Peripheral blood mononuclear cells from 15 adults, 10 normal newborns, 23 cord blood samples, and 11 patients with systemic lupus erythematosus were preincubated with Con A for 48 hr, irradiated, and added to a one-way mixed leukocyte culture. Adult Con A-activated cells suppressed the mixed leukocyte culture by 30 + 6.5%. By contrast cord cells and newborn cells had no suppressive activity; these cells resulted in stimulation of 18 + 12.1 and 18 + 7%, respectively. This lack of suppression also was present in systemic lupus erythematosus cells (11.2 + 13.3). The supernatants of both Con A sepharose-stimulated cord and adult cells showed significant suppressive activity and there was some suppressive activity of sepharose-stimulated cells alone. These results suggest that the mixed leukocyte cultures suppressive activity observed previously by newborn cells is radiosensitive and dependent on ongoing cell division for its expression. It also is independent of prior mitogenic stimulation. (Pediatr Res 19: 927-929, 1985) neonatal T cells also inhibit the proliferation of and immunoglobulin synthesis by neonatal and adult B cells (6).Con A has been used to selectively activate normal adult suppressor T cells (7,8). Using this procedure, deficient suppressor cell activity has been noted in patients with certain human autoimmune diseases, particularly SLE (7, 9). Williams and Korsmeyer (10) have shown that supernatants from Con Astimulated human cord blood lymphocytes inhibit the MLC response. Abedin and Kirkpatrick (1 1) reported that both cord blood cells and cell supernatants suppressed antigen and mitogen-induced proliferation of adult T cells even without prior mitogenic activation, implying a high degree of spontaneou~s suppressor activity.The present studies sought to identify functional differences between adult and newborn suppressor activity. We postulated that Con A-treated irradiated newborn lymphocytes and theilr supernatants would demonstrate more suppression than adult cells. To our surprise, we found that Con A-activated newborn cells had less suppressive activity than adult cells, and that while the supernatants did exhibit some suppressive activity, this wals independent of the presence of Con A. We believe these resul1.s indicate that neonatal T suppression requires active cell division for its expression. METHODS AbbreviationsSubjecrs. We studied cells from 15 normal adult controls agcs 25 to 50 yr, 23 freshly obtained cord blood specimens, I0 normal MNC, mononuclear cells newborns 24 to 72 h of age, and I 1 patients with SLE. The latter MLC, mixed leukocyte culture included nine females and two males aged 21 to 59 years, f0u.r Con A, co...

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“…It must be emphasized that this comparison does not reflect the number of T cells responding to the entire spectrum of alloantigens, but rather the frequency of T lymphocytes that can respond to the alloantigens expressed by a single unrelated individual. It has previously been demonstrated that the frequency of alloreactive T cells does not increase after birth (30). Thus, the autoreactive population appears to have been selectively contracted compared to the alloreactive population, implying that the T-cell repertoire has been shaped by the clonal elimination of some but not all autoaggressive cells.…”

Section: Methodsmentioning

confidence: 92%

Generation and regulation of autocytotoxicity in mixed lymphocyte cultures: evidence for active suppression of autocytotoxic cells.

Rosenkrantz¹,

Dupont²,

Flomenberg³

1985

Proc. Natl. Acad. Sci. U.S.A.

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Using limiting dilution analysis, we have detected both the generation and suppression of autocytotoxic cells following autologous or allogeneic stimulation in vitro. Assay conditions were established in which the cytotoxic response toward an allogeneic sensitizing cell was consistent with a traditional single-hit kinetic model. Under identical conditions, cytolytic activity toward autologous phytohemagglutinin-activated lymphoblasts exhibited a distinct biphasic response. At low responder cell doses, a clear autocytotoxic response was observed. However, at higher responder cell numbers, this autocytotoxic reaction disappeared. This biphasic pattern of autocytotoxicity developed after stimulation with allogeneic or autologous peripheral blood mononuclear leukocytes (PBL) or Epstein-Barr virus-transformed B cells. This pattern of response is consistent with the counterpoised actions of two distinct cell populations, an autoaggressive population and a lower frequency autosuppressor population. Autocytotoxicity was not the result of mitogenic or xenogeneic antigenic stimulation, as it was observed after stimulation with autologous PBL in autologous serum and an autologous interleukin 2 preparation. Thus, cells capable of autocytotoxicity are present in peripheral blood but at a lower frequency than allocytotoxic T lymphocytes. Furthermore, autoaggressive cells are downregulated by an autologous suppressor population. These findings suggest that immunologic self-tolerance is, at least in part, an actively maintained condition. Disturbances in this autoregulatory network may have relevance to the pathogenesis of some autoimmune diseases and graft-versus-host disease.

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Response of Human Newborn Lymphocytes to Alloantigen: Lack of Evidence for Suppression Induction

Cited by 11 publications

References 7 publications

Human Growth

Human Growth

Lack of Suppression by Concanavalin A-Activated Neonatal Mononuclear Cells

Generation and regulation of autocytotoxicity in mixed lymphocyte cultures: evidence for active suppression of autocytotoxic cells.

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