Search PubMed⌕ Search

Biomedical subjects

H M Etlinger

Publications and source records attributed to H M Etlinger.

36 records · Page 2Linked to original sources

Maturation of the lymphoid system. IV. Ontogenetic compartmentalization of T cell function.

Pretreatment of one day old but not eight day old or adult A/J mice with soluble ovalbumin (OVA) initiated specific T-cell unresponsiveness as reflected both in T-cell dependent cellular proliferation and in anti-hapten antibody responses to dinitrophenyl-OVA. In contrast, injection of soluble human gamma globulin into either neonatal or adult A/J mice resulted in unresponsiveness. The ability of lymph node T-cells to be sensitized by protein antigens occurred shortly after birth, since the degree of sensitization in 9 and 26 day old mice was similar. Finally, a striking ontogenetic difference was noted in the capacity of lymphocytes derived from the lymph nodes and spleens of young mice to respond to T-cell mitogens. Thus, while splenocytes obtained from 9 day old mice exhibited meager responses to PHA and Con A, lymph node cells from these animals responded at nearly adult levels. These observations are interpreted as reflecting an ontogenetic and tissue-specific division of T-cell function.

Age Factors↗

Maturation of the lymphoid system. III. Induction of selective unresponsiveness by injection of a haptenated carbohydrate into neonatal mice.

Neonatal treatment of A/J mice with DNP-Ficoll reduced or eliminated indirect anti-DNP PFC normally produced in response to adult challenge with DNP-keyhole limpet hemocyanin. The remaining direct anti-DNP PFC response was of low avidity. Spleen cells from neonatal A/J mice inhibited the in vitro but not the in vivo response of adult spleen cells to DNP-Ficoll.

Animals↗

Expression of a distinct B cell clonotype profile after recovery from antigen-induced unresponsiveness.

The purpose of these experiments was to determine whether the B cell clonotype profile expressed in mice which have recovered from antigen-induced unresponsiveness is similar to that of nontolerized mice. Unresponsiveness to phosphorylcholine (PC) was initiated by injection of neonatal mice with PC-coupled human gamma globulin, resulting in the inability to respond to challenge with PC-lipopolysaccharide at 1.5 months of age. By 3 months of age, pretreated mice were 50% responsive while by 5 and 7.5 months of age, full responsiveness was observed. At each time point two differences distinguished the anti-PC antibody from nonpretreated mice. First, whereas nonpretreated mice displayed T15 dominance, pretreated mice did not. Second, the average avidity of T15-negative antibody produced in pretreated mice was greater than that in nonpretreated mice and similar to that of T15-positive antibody. Possible mechanisms for this "permanent" alteration of the antibody profile are discussed.

Aging↗

Maturation of the lymphoid system. I. Induction of tolerance in neonates with a T-dependent antigen that is an obligate immunogen in adults.

A/J mice displayed a striking ontogenetic difference in the capacity to respond to DNP-Ficoll, a T-independent antigen, and to aggregated human gamma-globulin (AHGG), a T-dependent antigen. Thus, whereas responses to DNP-Ficoll of 4-day-old mice were similar in magnitude to those of adult animals, responses to AHGG did not become pronounced until mice were some 30 to 40 days of age. The inability of young animals to respond to AHGG was reflective of a negative consequence of lymphocyte/antigen interaction, since such mice became specifically unresponsive to subsequent challenges with AHGG. Unresponsiveness induced by neonatal injection of AHGG lasted 50 to 60 days, in contrast to that induced by deaggregated HGG, which persisted some 100 days longer. The unresponsive state induced by injection of neonates with AHGG maintained itself upon adoptive transfer and did not appear to be linked to suppressive factors associated with either serum or lymphoid cells for its maintenance. Finally, AHGG was also shown to be capable of inducing unresponsiveness in neonatal, athymic mice. These results demonstrate that AHGG, the normally immunogenic form of HGG in adult mice, can serve as an effective tolerogen when administered into a neonatal environment.

Aging↗

Maturation of the lymphoid system. II. Characterization of the cellular levels of unresponsiveness induced in neonates by a T-dependent antigen that is an obligate immunogen in adults.

It has previously shown that AHGG, a form of HGG that is highly immunogenic in euthymic adult mice, is capable of inducing specific unresponsiveness when injected into neonatal animals. This report extends this finding and indicates that such a neonatal treatment results in the induction of tolerance in T as well as B cells. Furthermore, a similar conclusion was reached regarding specific T lymphocyte function in animals treated as neonates with OVA. The ability of LPS to modulate responses of neonatal animals to AHGG or DHGG was also examined. It appeared that such mice were not susceptible to the adjuvant effects of LPS until the 4th week of life. Furthermore, LPS was incapable of inhibiting the unresponsiveness induced in mice by either DHGG or AHGG until the 3rd or 4th week of life.

Animals↗

Studies on the question of conventional immunoglobulin on thymocytes from primitive vertebrates. I. Presence of anti-carbohydrate antibodies in rabbit anti-trout Ig sera.

An unexpected cross-reactivity between trout immunoglobulin (Ig) and keyhole limpet hemocyanin (KLH) was observed. Rabbit antisera to KLH were capable of binding to radioiodinated trout Ig and, conversely, antitrout Ig reacted with KLH. The cross-reactive antibodies were not found in preimmune sera and did not arise because of a common contaminant in the two immunizing preparations. The molecular basis of the cross-reactivity was found to reside in the carbohydrate moieties. Isolated glycopeptides from KLH and trout Ig were efficient inhibitors of the cross-reactivity. Furthermore, L-fucose was capable of inhibiting the cross-reactivity, whereas other monosaccharides tested did not. Absorption of anti-KLH with trout Ig and anti-trout Ig with KLH effectively removed the cross-reactive antibodies and only slightly affected the titer to their respective homologous antigens. Antibodies with specificity for L-fucose were isolated from anti-KLH and anti-trout Ig sera by passage over affinity columns and elution with the monosaccharide.

Absorption↗

Evolution of the lymphoid system. II. Evidence for immunoglobulin determinants on all rainbow trout lymphocytes and demonstration of mixed leukocyte reaction.

Indirect fluorescent antibody analyses utilizing antiserum specific for rainbow trout serum immunoglobulin (Ig) demonstrated that essentially all rainbow trout lymphocytes from thymus, spleen, anterior kidney and peripheral blood possess either Ig determinants or structures which cross-react with those determinants found on serum Ig. Peripheral blood leukocytes from rainbow trout were found to be caple of participating in a mixed leukocyte reaction. This observation is discussed in terms of the evolution of T cell function.

Animals↗

Suppression of immunological activities by mouse amniotic fluid.

Mouse amniotic fluid (MAF) was shown to be capable of suppressing those antibody responses observed in euthymic or athymic mouse spleen cell cultures to the T-independent antigens dinitrophenylated Ficoll (DNP-Ficoll) and trinitrophenylated lipopolysaccharide (TNP-LPS) and to the polyclonal B-cell activators LPS and purified protein derivative of tuberculin (PPD). Titration experiments demonstrated that the suppressive capacity of MAF for either LPS or DNP-Ficoll responses was maintained up to a MAF dilution of 1:120. Preincubation of spleen cells obtained from athymic mice with MAF for 8 h significantly suppressed polyclonal B-cell activation of such cells induced by LPS, although suppression was greater when MAF was present during the entire culture period. In addition, the suppressive activity that MAF demonstrated for antibody production induced by DNP-Ficoll or LPS was not lost as a result of dialysis. MAF also suppressed the secondary in vitro proliferative responses of lymph node cells sensitized to the T-dependent antigen human gamma globulin (HGG). HGG-induced proliferation of such cells appeared to be more susceptible to suppression effected by MAF than concanavalin-A-induced proliferation.

Amniotic Fluid↗

Lymphocyte specificity to protein antigens. I. Characterization of the antigen-induced in vitro T cell-dependent proliferative response with lymph node cells from primed mice.

An in vitro assay which measures antigen-induced proliferation of primed murine lymph node cells is described. The response is mediated by T eclls since it can be obtained by using nylon wool-passed lymphocytes (less than 1% Ig+ cells) and it can be abolished by treatment with anti-Thy 1.2 and C. Furthermore, LN cells from nu/nu mice injected with antigen do not demonstrate antigen-induced proliferation in contrast to the response observed in euthymic littermate controls. Other relevant parameters of this proliferative assay include the observations that the response is highly antigen specific, can be seen as early as 4 days and as late as 60 days after in vivo priming, is restricted to the use of certain sets of LN when animals are injected subcutaneously at the base of the tail, and can be seen with LN cells from mice primed with antigen in either CFA or ICFA. The ease of the assay coupled with its specificity and quantitative dimensions provides a direct and simple method to evaluate processes involved in antigen-induced murine T lymphocyte activation.

Animals↗

Rainbow trout leukocyte culture: a simplified method.

The addition of 10% fetal bovine serum to Leibovitz's L-15 culture medium resulted in marked growth of peripheral blood leukocytes from rainbow trout, Salmo gairdneri. Culture medium without serum or with 20% homologous serum did not induce substantial growth. In contrast to what has been reported by others, oxygenation of the culture medium was found not to be required for excellent cell growth.

Animals↗

Evolution of the lymphoid system. I. Evidence for lymphocyte heterogeneity in rainbow trout revealed by the organ distribution of mitogenic responses.

Leukocytes from the various lymphoid tissues of rainbow trout (RBT) were tested for their capacity to respond to the lymphocyte mitogens concanavalin A (Con A), lipopolysaccharide (LPS), and purified protein derivative of tuberculin (PPD). Thymocytes responded to Con A but not to LPS or PPD. In contrast, leukocytes from anterior kidney were stimulated with LPS but not with Con A or PPD. Cells from spleen and peripheral blood were stimulated by each mitogen. However, the degree of stimulation at optimally stimulatory concentrations of each mitogen was distinctive. The finding that the patterns of mitogenic responses of cells from each tissue were significantly different suggested that there is lymphoid heterogeneity in the RBT with a unique tissue distribution. The species source of serum utilized as a medium supplement appeared to be capable of markedly affecting mitogenesis. Thus, LPS and PPD stimulation occurred in medium supplemented with rainbow trout serum (RBTS). On the other hand, LPS and PPD stimulation was not observed in medium supplemented with fetal bovine serum (FBS), with the exception of peripheral blood leukocytes which were stimulated by LPS in culture medium supplemented with FBS. Con A stimulated leukocytes from each lymphoid tissue in medium supplemented with RBTS and, with the exception of cells from anterior kidney, also stimulated cells from each tissue in medium supplemented with FBS. The kinetic profiles of the responses of peripheral blood leukocytes to Con A, LPS, and PPD suggested that the extent as well as the time required for maximal stimulation was dependent on the dose of mitogen.

Animals↗