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In the previous paper we showed that the immune response to sheep red cells (SRBC) was degenerate; serum antibodies showed increasing loss of specificity, signalled by cross-reactions with horse RBC (HRBC), with time after immunization and with hyperimmunization. In the present report we have analysed the role T cells may play in this process. To do this we studied the antibodies made by mice deprived of T cells by irradiation as well as those made by normal mice immunized with SRBC in distilled water, which was shown to depress the DNA synthetic response of T cells. In both instances the mice with fewer responding T cells made less antibody which could agglutinate HRBC than did the appropriate controls. This was true even when no difference in anti-SRBC titre was apparent. In addition we showed that the antibody made by mice with reduced numbers of T cells was less effective at passive suppression of the immune response to SRBC than was similarly titred (against SRBC) antibody made by normal mice. Thus, certain sub-populations of antibodies, normally made in response to SRBC, immunization, are particularly thymus dependent. We have discussed why we think they are those of particularly high affinity. [ABSTRACT FROM AUTHOR]

Bone marrow cells and thymus cells were observed in cell transfer expehments to collaborate in the production of anti-BSA antibodies. The target cells for tolerance induction either with a 'low dose' of antigen (100 µg of deaggregated BSA once a week × 5) or with a 'high dose' (a single injection of 5000 µg) were identified by the same technique. In 'low dose' tolerance, some indication was obtained that thymus-derived cells in peripheral lymphoid systems were the target cells; bone marrow-derived cells appeared not to be so susceptible, and the cells residing in thymus or bone marrow seemed to remain unimpaired, in contrast, the injection of a 'high dose' of tolerogen rendered both types of cells in spleen, thymus cells and bone marrow cells, unresponsive or hyporesponsive in parallel with one another. [ABSTRACT FROM AUTHOR]

Bone marrow-thymus cooperation experiments were carried out in lethally irradiated mice with sheep red blood cells (SRBC) as the antigen and direct plaque-forming cells (PFC) as the end point. Various parameters were altered, with the following results: (1) Above 800 rad, the response by marrow cells alone, as well as the increase due to added thymus cells, was independent of irradiation dose. (2) The response of marrow cells was greatest at high SRBC concentrations, but the co-operative effect of thymus cells was most evident at lower SRBC levels, and completely absent at high levels. (3) Increasing the number of marrow cells, without thymus, gave increasing numbers of PFC, but the dose-response curve did not suggest cell synergism. (4) Thymectomy and antithymocyte serum treatment of host or donor did not prevent the response by marrow cells alone. It was concluded that this was a true IgM response by antibody-forming precursors from the marrow, unaided by thymus-derived cells. [ABSTRACT FROM AUTHOR]

The peak of blast response in primary, one-way mixed lymphocyte culture of CBA plus DBA/2m took place on culture day 6 to 7, whereafter the number of blasts per culture declined. Concomitanlly with the disappearance of blast cells from these cultures, the number of lymphocytes increased, indicating that a certain number of blasts reverts back to lymphocytes ("secondary lymphocytes"). The number of antigen- reactive tells in primary mixed culture (quantitated by hydroxyurea block) was on the order of 3% to 5%, whereas when the same cultures were reprimed with the original antigen, the number of antigen-reactive cells was on the order of 90%. Thus most lymphocytes surviving prolonged primary mixed lymphocyte culture are in fact secondary lymphocytes--that is, blast-derived. The secondary lymphocytes thus obtained responded promptly and in a biphasic manner to the original and H-2 cross-reactive stimulator cells in secondary mixed culture. The first, major response peak took place on culture day 2 to 3 and the second, minor peak on culture day 5 to 6. Although the secondary lymphocytes were sensitive to anti-0 plus complement, they did not respond to phytohemagglutinin. The secondary lymphocytes were themselves cytotoxic to relevant allogeneic target cells in vitro, and they were promptly reinduced to maximal cytotoxicity by a second priming with the original antigen. We suggest that these functions are characteristic to T memory cells primed against histoincompatible cells. [ABSTRACT FROM AUTHOR]

The response of human peripheral lymphocytes to phytohemagglutinin-, concanavalin A-, pokeweed mitogen-, and mitomycin-treated allogeneic lymphocytes was characterized according to the surface markers of the responding cells. Almost all blast cells derived from these cultures could be classified as either B or T cells. Phytohemagglutinin, concanavalin A, and allogeneic lymphocytes triggered exclusively T-cell stimulation, whereas pokeweed mitogen gave rise to a dual response. No shift in the proportion of responding B and T cells was found at different concentrations of pokeweed mitogen under the present conditions. Purified T cells, isolated by sheep erythrocyte (SRBC) rosette sedimentation, responded slightly more strongly than unseparated cells, whereas purified non-SRBC-binding cells were essentially unresponsive to all three lectins. The presence of monocytes was found to increase the lectin responses as well as to make them more reproducible. It is suggested that the classification of proliferating lymphocytes by surface markers may yield clinical information as well as serve as a useful tool in the evaluation of in vitro cellular cooperation. [ABSTRACT FROM AUTHOR]

Cell-mediated lysis of target monolayers infected with lymphocytic choriomeningitis virus has previously been shown to be a property of specifically sensitized thymus-derived lymphocytes (T cells). The cytotoxic potential of individual effector lymphocytes is maximally expressed when infected monolayers are confluent and overlaying immune spleen cells cover less than the total target area. The data presented support the following interpretations: [1] Cell-mediated injury depends on close association between sensitized T cells and infected L cells. [2] Any attachment made is readily reversible. [3] Effector lymphocytes may damage more than one target cell, operating, perhaps, in a rather circumscribed area. [4] Cell death is a 'one hit' phenomenon. [5] Cytolysis is a property of individual T cells, there being no obvious requirement for co-operation between different populations of spleen cells. [6] Substances secreted into the medium at large are neither directly cytotoxic nor capable of sensitizing normal spleen cells. [7] Specific lysis occurs at temperatures ranging from 27°C to 40°C, being maximal at the higher temperature. [ABSTRACT FROM AUTHOR]

CBA lymphocytes were primed in one-way mixed lymphocyte culture by DBA/2 under conditions where only T cells proliferate, and the blast cells were recovered on the sixth culture day by fractionation in 1-g velocity sedimentation. When placed on a syngeneic (to responder cells) feeder layer, the blasts reverted to lymphocytes ('secondary lymphocytes'). Two functions, dissimilar from nonprimed T cells, were defined for the secondary lymphocytes: they were cytotoxic to relevant allogeneic target cells in vitro, and they responded promptly to the original stimulator cells in secondary mixed lymphocyte culture. These properties were then used to define the rate of recovery of the activated cells in the blast fraction. CBA lymphocytes were similarly primed by DBA/2, three fractions were recovered (blasts, intermediate-sized lymphocytes, and small lymphocytes), and the cells from each fraction were plated on syngeneic feeder layer. Only the progeny lymphocytes of the blast cells displayed the altered responses. Thus all, or almost all, activated cells may be selectively recovered in the blast fraction on the sixth day of one-way mixed lymphocyte culture. [ABSTRACT FROM AUTHOR]

Supernatants from allogeneic spleen cell mixtures contain factors that replace both thymus-derived lymphocytes and adherent macrophage-equivalent cells in the in vitro primary antibody response to sheep erythrocytes. The making of these cell-replacing products requires the initial presence of allogeneic thymus-derived lymphocytes, but the final producer appears to be the adherent cell. Inhibition of DNA synthesis of allogeneic spleen cell mixtures prevents formation of these cell-replacing factors. It is the late maturation processes leading to the formation of highrate antibody-producing cells among the antigen-specific bone marrow-derived splenic lymphocytes that are amplified by soluble products from supernatants of allogeneic spleen cells, because such supernatants are most active when added to purified splenic bone marrow cells that have been in contact with antigen for 48 hr. Both these early and late maturation processes of splenic bone marrow cells are sensitive to mitomycin C and require the continuous presence of antigen. A model is presented where activated thymus-derived lymphocytes alarm macrophages to secrete a product that helps bone marrow-derived lymphocytes that have been in primary contact with antigen to develop and mature into high-rate antibodyforming cells. [ABSTRACT FROM AUTHOR]

After neuraminidase treatment the electrophoretic mobility of mouse lymphocytes (B and T cells) and thymocytes was reduced to a similar value, a diminution of about 40%, 60%, and 40%, respectively. Thus B and T cells and thymocytes may have a common surface charge after removal of sialic acid. The percentage of cells binding anti-thymocyte serum was not changed; thus sialic acid does not seem to be an important part of the specific antigen of lymphoid cells. Similar amounts of sialic acid were released from B and T cells, whereas less than half of this was released from the thymocytes. Thus, whereas thymocytes are characterized by their low electrophoretic mobility and low sialic acid release and T cells by high electrophoretic mobility and high sialic acid release, B-cells in contrast show a low electrophoretic mobility and high sialic acid release. [ABSTRACT FROM AUTHOR]

In mice with meningitis induced by ectromelia virus, the influx of inflammatory cells into cerebrospinal fluid (CSF) was shown to be triggered by an immunologically specific, T cell-dependent mechanism. These cells were counted, and their cytotoxicity assayed in vitro. Cell numbers reached a peak 6 days after infection and showed specific cytotoxicity for ectromelia-infected target cells, an effect that reached a peak at day 6 and was retained for at least a further 4 days. Treatment with anti-thymocyte serum 2 to 3 days before harvest of CSF cells depressed the numbers found and their cytotoxicity, suggesting that they reached the exudate from the blood. [ABSTRACT FROM AUTHOR]

The cytotoxicity of human peripheral blood lymphocytes (PBL), after a 6-day allogeneic stimulation in unidirectional mixed lymphocyte culture (UMLC), was studied. PBLs stimulated with phytohemagglutinin (PHA) and labeled with 51Cr were used as target cells. The effector cells were incubated with the target cells at a 100:1 ratio for 6 hr. The amount of isotope released into the supernatant was used to calculate lysis. Cell-mediated lympholysis (CML) was specific, as shown by an innocent-bystander experiment and by the lack of lysis of target cells autologous with the effector cells. The specific lysis had the following features: linear increase between 2 and 8 hr of incubation, linear increase with the logarithm of the number of effector cells, and inhibition by EDTA and by cytochalasin B. Under the UMLC conditions used, potent effector cells were present already on day 4. A reduction in the number of stimulating cells to one third of the number of responding cells in UMLC resulted in a decrease of thymidine incorporation and in an increase of CML. The significance of CML for transplantation biology is discussed. [ABSTRACT FROM AUTHOR]

Injection of neonatal Balb/c or C57B1/6 mice with (C57B1/6x Balb/c)F1 lymphoid cells leads to transient chimerism and runting, and to splenomegaly, deficient T-cell function and a gradual replacement of lymphoid organs with abnormal reticular cells. Activated MuLV can be isolated from such mice. It is proposed that either graft-versus-host or host-versus-graft allogeneic reactivity activates endogenous MuLV virus, which then causes functional and morphological abnormalities in the lymphoid organs. [ABSTRACT FROM AUTHOR]

By using T cell-deprived mice and appropriate controls it has been shown that the adjuvant activity of LPS on the immune response to different doses of SRBC, tends to be oriented more towards B cells than towards T cells. In contrast, lentinan seems to mediate its adjuvant activity largely through a stimulatory effect on helper T cells. [ABSTRACT FROM AUTHOR]

A surface immunoglobulin (Ig) has been extracted from E14, a tissue culture established mouse T-cell lymphoma. The purified protein can be separated into heavy and light chains by reduction with 2-mercaptoethanol. The intact Ig has a molecular weight of 170,000 and the heavy chain has a molecular weight of 64,000. [ABSTRACT FROM AUTHOR]

The response of mouse spleen cells to the T cell-independent antigen dinitrophenylated polymer of flagellin (DNP-POL), has been studied using an adoptive transfer system, and compared with the response of bone marrow cells. Spleen cells showed a complex cell dose-response relationship, with a markedly discontinuous curve, for assays performed before day 9 after transfer and antigen challenge. This discontinuity could be explained by a delay in attainment of the peak response for lower cell inocula. The curve became linear on a log-log scale when spleens were harvested on days 9 and 10 post-transfer. Bone marrow cells gave a lower response than would be expected from their lymphocyte content. This response increased progressively with a delay before antigen challenge in the irradiated recipient or in tissue culture prior to cell transfer, suggesting a functional maturation in this cell population, whereas the performance of spleen cells fell off under similar circumstances. The findings were consistent with, but could not prove, the hypothesis that the immediate precursors of anti-DNP antibody-forming cells in bone marrow were high surface immunoglobulin density small lymphocytes that had arisen locally from precursors lacking detectable surface immunoglobulin, by a non-mitotic maturation. [ABSTRACT FROM AUTHOR]

The target cell of in vitro stimulation of primed spleen cells by hapten-carrier complexes was studied. The antigens DNP28-bovine serum albumin (DNP28-BSA), which gives only 2,4-dinitrophenyl (DNP) specific responses and DNP14-mouse immunoglobulin (DNP14-MIg), which probably reveals DNP as well as carrier specificity (new antigenic determinant) were used. Educated T cells could be stimulated with the antigens used for activation. A similar experiment with educated B cells, however, gave no indication that these B cells could be stimulated with antigen in the absence of T cells. Cortisone treatment of primed mice yielded spleen cells which had a higher activity than spleen cells from unprimed, cortisone-treated mice. This also points to stimulation oft cells by antigen. Treatment of primed spleen cells with anti-thymocyte serum (ATS) and complement (C) abolished stimulation by phytohaemagglutinin (PHA) completely, by lipopolysaccharide (LPS) slightly, while the antigenspecific activity was 90 per cent reduced. This indicates a mainly T cell-specific stimulation by the antigen. A corresponding experiment with anti-plasma cell serum (APCS) and C revealed a complete reduction of LPS activity and a small impairment of the PHA and conavalin A (Con A) activity. However, the antigenspecific activity was reduced by one-third to a half for the different antigens. This is an indication for a specific B-cell stimulation by the antigen, although it is on a lower level than the T-cell stimulation. The role of the hapten in the T-cell stimulation is discussed. [ABSTRACT FROM AUTHOR]

The aim of the experiments was to find a T cell-mediated cytotoxic reaction where genetically determined low responsiveness is under the control of recessive genes. The T cell-mediated immune response to DBA/2 mastocytoma cells P 815-X2 in different inbred strains, F1 hybrids and congenic resistant strains of mice was determined using the 51Crk-release method. Two types of low responsiveness were found. The first already well documented type is characterized by dominance of low responsiveness in genetical analysis. It is due to tolerance because of the identity of the H-2 linked specificities of the recipient and of DBA/2 (H-2d) mice from which the turnout is derived. The second and new type of low responsiveness in T cell-mediated immunity was found in DBA/1 mice. In this strain low responsiveness is inherited as a recessive trait. The cytotoxic response of DBA/1J mice against the C57B1/6 lymphoma EL 4 is normal. Thus, their low responsiveness is restricted to a limited number of membrane determinants. [ABSTRACT FROM AUTHOR]

Supernatants were obtained from cultures of keyhole limpet haemocyanin (KLH) primed mouse spleen cells, and also from cultures of KLH-educated, thymus-derived lymphocytes (T cells) after re-exposure of cells to the original priming antigen, KLH. These supernatants were able to facilitate the immune response of bone marrow-derived lymphocytes (B cells) to sheep erythrocytes (SRBC). Certain physical and biological properties of such supernatant activities are described. [ABSTRACT FROM AUTHOR]

Thymus-dependent cells from thymus and peripheral lymphoid organ were preparatively separated by mean of free flow electrophoresis into various subpopulations which were defined in terms of θ (theta) antigen content, negative surface charge, graft-versus-host (GvH) reactivity, hydrocortisone sensitivity, cell volume and morphological details. Most thymocytes in the cortex have a low negative surface charge, high θ antigen content, are hydrocortisone-sensitive and immuno-incompetent. On the basis of electronic cell sizing this group consists of large population of 90 μm³ cells (T1) and a small population of 175 μm³ cells (T2), the latter being less hydrocortisone-sensitive than the former. A minority of thymocytes resides in and around the medulla and has high negative surface change, a medium θ antigen content, is hydrocortisone-resistant and reveals low GvH reactivity. These cells are medium sized (125 μm³)1 electrophoretically bimodal (T3 had a medium and T4 a high negative surface charge) and on the basis of morphological criteria are metabolically more active than the thymocytes of low negative surface charge. In the peripheral lymphoid organs, all thymus-dependent cells show high negative surface charge and have the lowest observed θ antigen content and the highest observed GvH reactivity. These cells fall into two populations of which one is 125 μm³ with lower negative surface charge and the other is 90 μm³ with a somewhat higher negative surface charge. These 125 μm³ cells (T4), which morphologically resemble the 125 μm³ thymocytes, are less GvH-reactive than the 90 μm³ (T5) cells, which seem to be resting cells. On tile basis of these data, a possible sequence of steps in the maturation of T cells was constructed as follows: in the cortex of the thymus T1 thymocytes are transformed into T2 and these develop into T3 and T4 thymocytes which have higher negative surface charge, lower θ antigen content and are in an advanced stage of maturity. After further loss of θ antigen these cells, which are in the medulla, emigrate into the periphery and are finally transformed into highly immunocompetent T5 cells possessing the highest observed negative surface charge. [ABSTRACT FROM AUTHOR]

We studied the effect of passively administered anti-carrier arid anti- hapten antibodies on the primary anti-hapten antibody response to hapten-carrier conjugates in mice. Bacterial α-amylase (BαA), Taka-amylase A (TAA) and key-hole limpet haemocyanin (KLH) were used as carrier molecules, and 2,4-dinitro-phenyl (DNP) group was used as a haptenic determinant. Three groups of mice were injected intravenously with anti-carrier antiserum, anti-hapten antiserum and normal serum as the control, respectively, immediately after the immunization with the hapten-carrier conjugate. The primary anti-carrier antibody response was markedly suppressed by the passively administered anti-carrier antibody but not anti-hapten antibody. However, the primary anti-hapten antibody response was suppressed not only by passively administered anti-hapten antibody but also by the injection of anti- carrier antibody in an early period after the immunization. When anti-carrier antibody was given twice 0 and 7 days after immunization, the primary anti-hapten antibody response was markedly suppressed and the suppressive effect was observed even at a later period. In contrast, anti-hapten antibody given by the same schedule as above suppressed only the primary anti- hapten antibody response, but not the anti-carrier antibody response. Passively administered anti-carrier antibody did not suppress carrier-specific helper cell development, but still suppressed the development of B memory cells and antibody formation against carrier determinants. The antigen dose required for the development of B-cell memory was much higher than that necessary for the stimulation of' T cells. Passively administered anti-carrier antibody clearly inhibited the cellular cooperation between carrier-committed helper cells and hapten-specific B cells and the augmented primary anti-hapten antibody response induced by carrier-primed T cells was clearly abolished. Furthermore, mice preimmunized with carrier showed significantly lower anti-hapten antibody response following the hapten- carrier challenge. Moreover, development of hapten-specific memory cells was also suppressed. Thus, even in the non-specific antibody-induced suppression by anti-carrier antibody, negative feedback effect of a B-cell product with anti-carrier specificity exclusively regulates the B-cell line development and differentiation. [ABSTRACT FROM AUTHOR]

The differentiation of the guinea-pig thymus and thymocytes was studied using alkaline phosphatase (AP) as a marker of the thymocytes. The stem cell was assumed to be AP-negative. Cortical thymocytes contained a high activity of AP, which was lost or greatly diminished during the differentiation into medullary thymocytes and into T cells. Only approximately 1 per cent of the peripheral lymphocytes contained AP-activity. The role of these cells is obscure. In the morphological study three developmental stages were observed. At the beginning the AP-activity was concentrated in the periphery of the thymus anlage, and was first observed in a 23-day-old foetus. At about 28 days the foetal thymus contained homogeneously distributed AP-positive and AP-negative cells. The cortex and medulla began to differentiate at the age of 31-33 days and the definite differentiation formed the third developmental stage. Medulla achieved its maximal proportion at birth. The results are in agreement with earlier studies concerning the development of the guinea-pig thymus. [ABSTRACT FROM AUTHOR]

Infection of Escherichia coli cells with the transducing phage φ80psu3+ causes phage-dependent synthesis of su3+ tyrosine tRNA. This report describes the effect of superinfecting T4 phages on the expression of a single E. coli tRNA gene, namely the φ80 phage integrated su3+ tyrosine tRNA gene, and provides evidence that T4 phage-induced alteration of the DNA-dependent RNA polymerase is sufficient to stop E. coli gene transcription, 1. The mutual effects of φ80psu3+ and T4 amN82 phages on their multiplication in E. coli BF266 are as follows: simultaneous infection results in a complete mutual inhibition of phage multiplication; T4 amN82 phage superinfection within 45 min after φ80psu3+ infection has the same result T4 amN82 phage superinfection later than 45 min after φ80psu3+ phage infection does not affect φ80psu3+ phage multiplication. In all cases of superinfection no viable T4 amN82 phages could be detected, whereas the φ80psu3+ phages multiplied or survived without multiplication. 2. The φ80psu3+-dependent su3+ tyrosine tRNA synthesis is immediately and absolutely inhibited upon T4 amN82 phage superinfection. The cause of this inhibition is not a selective degradation of the φ80 phage-incorporated su3+ tyrosine tRNA gene, since it could be demonstrated that φ80 phages isolated from lysates of φ80psu3+/T4 amN82 superinfected E. coli cells still carried the suppressor gene. 3. The inhibition of φ80psu3+ phage-dependent su3+ tyrosine tRNA synthesis upon T4 amN82 phage superinfection was also observed if the superinfection with T4 amN82 occurred during inhibition of protein biosynthesis. 4. Superinfection of φ80psu3+ phage-infected E. coli BF266 cells with T4 amN82 ghosts did not inhibit φ80psu3+ phage-dependent su3+ tyrosine tRNA synthesis. 5. The results described above provide evidence that the inhibition of φ80psu3+-dependent su3+ tyrosine tRNA synthesis upon T4 amN82 phage superinfection is most likely caused by the T4 phage-induced alteration of the E. coil DNA-dependent RNA polymerase. [ABSTRACT FROM AUTHOR]

The study concerned the binding of sheep red blood cells by human peripheral blood lymphocytes. The results indicate that the phenomenon (rosette formation) is probably dependent on thymus-derived lymphocytes (T lymphocytes) and not due to bone marrow lymphocytes (B lymphocytes). These data were obtained by a gradient centrifugation technique separating B lymphocytes from rosette-forming cells, by direct study of B lymphocytes and rosette-forming cells in the same preparations, and from the study of patients with selective immunodeficiency diseases and chronic lymphocytic leukaemia. Furthermore, inhibition of rosette formation was absent or very weak after incubation of lymphocytes with anti-immunoglobulin antisera, but considerable following their incubation with unspecific mitogens (phytohaemagglutinin, pokeweed mitogen, concanavalin A, anti-lymphocyte antiserum) and also after trypsin treatment. Incubation temperature was important for the frequency of rosettes, and experiments with metabolic inhibitors showed that to form rosettes the lymphocytes required an intact energy production. [ABSTRACT FROM AUTHOR]

Delayed-type hypersensitivity (DTH) to Salmonella polymerized flagellin (POL) was transferred to normal and Iethally irradiated CBA mice by POL-activated thymus-derived (T) cells or by lymphoid cells rich in T cells from POL-primed donors, but not by POL-activated bone marrow-derived (B) cells or by serum from POL-primed donors. It was therefore concluded that T cells play a key role in the initiation of DTH reactions. T cells activated by POL of one specificity were equally able to transfer DTH to POL of the same or of another specificity. DTH to haemocyanin (HCY) (Jasus lalandii) was transferred only by HCY-activated T cells. Two interpretations of these findings are discussed: 1) that T cells may be less restricted in specificity than B cells, and 2) that T cells recognize a common antigenic determinant (carrier determinant) on the polymerized flagellins of Salmonella spp. which is not recognized by B cells. [ABSTRACT FROM AUTHOR]

The ability of thymus-derived (T) cells activated by polymerized flagellin (POL) from Salmonella adelaide to transfer anti-POL delayed-type hyper-sensitivity (DTH) to normal mice was largely abrogated by pretreating the cells with anti-Θ serum and complement, and completely abrogated by pretreating the cells with POL labelled with 125I-iodine to hight specific activity. The thymocyte precursors of POL-activated T cells were also in-activated by treatment with 125I-POL. T cells activated by POL of one specificity were completely inactivated by 125I-POL of the same or of another specificity but not at all by 125I-labelled haemocyanin (Jasus lalandii). Pre-incubation of POL-activated T cells with rabbit anti-mouse light chain globulin prevented their subsequent inactivation by 125I-POL but did not reduce their ability to transfer anti-POL DTH. The significance of these findings is discussed. [ABSTRACT FROM AUTHOR]

When nuclei from the lymphocytes of mice immunized with rabbit erythrocytes are injected into unprimed animals the number of cells forming antibody to rabbit erythrocytes increases to a level approaching that of the immunized donor animals. The specificity of the response induced by nuclei is equally as good as that induced by native antigen. When ‘T’ and ‘B’ mice are immunized with rabbit erythrocytes a poor response is observed but when the nuclei from primed ‘T’ animals are used to immunize ‘B’ mice the number of antibody-producing cells is very much increased. In view of current theories about cellular co-operation it is pointed out that this co-operative effect of ‘T’ lymphocyte nuclei is independent of both cell membrane and additional antigen. [ABSTRACT FROM AUTHOR]

Normal mouse serum confers on bone marrow rosette-forming cells (RFC) from normal mice a high sensitivity to anti-theta serum (AθS) and azathioprine (AZ) which they otherwise lack. Such an effect can also be demonstrated on spleen cells from adult thymectomized mice, `thymus-deprived' and nude mice, but the amount of serum required is higher in the latter mice. This activity of serum on RFC disappears after thymectomy of the serum donor with a half-life of 2.5 hours and reappears in thymectomized mice within 4 days after grafting of a thymus. Serum thymic activity (TA) is present in different amounts in different mouse strains and in ageing mice it progressively disappears. No TA is found in the serum of 4-week- old nude mice. TA is stable after lyophilization but is thermolabile in solution. It passes through UM 10 Amicon membranes, which suggests that its molecular weight (mol. wt) is probably < 10,000. TA is reversibly suppressed in the presence of a serum inhibitor with a mol. wt between 100,000 and 300,000. This inhibitor is not detectable in the serum of thymectomized mice unless the serum is incubated with TA containing serum for 60 minutes at 37°. The biological significance of TA is still a matter of speculation but its role in maturation or expansion of T-cells is suspected. [ABSTRACT FROM AUTHOR]

A micro-immune adherence assay employing direct microscopic observation was used to detect the presence of thymus-derived cell antigenic specificities on guinea-pig lymph node cells, purified peritoneal exudate lymphocytes, and thymocytes using a heterologous burro anti-guinea-pig thyrnocyte serum. A method is described for the direct determination of thymus-derived cell specificity of anti-lymphocyte sera. [ABSTRACT FROM AUTHOR]

Thymectomized, lethally irradiated, bone marrow reconstituted mice were treated with a large dose of sheep red blood cells (SRBC) over the course of 30 days. They were unable to respond to further antigenic challenge for one month. Fifteen million thymocytes given 4 days after the termination of treatment restored their ability to respond. The same antigenic treatment given to similar chimeras, which differed only in having had 15 × 106 thymus cells added to the bone marrow inoculum, also abolished the response to further antigenic challenge. In contrast to chimeras without thymus cells present during the course of treatment, the later addition of thymocytes to these animals did not restore their response. It did, however, restore the response to a second challenge of antigen given 17 days after the addition of thymocytes. This response was the same as non-treated animals given only one injection of thymocytes and significantly less than non-treated animals given thymocytes twice. The following explanation of these results is offered. Bone marrow derived (BMD) lymphocytes that can make antibody without assistance of thymus derived (TD) lymphocytes were made tolerant in the absence of TD cells. Thymus dependent BMD cells were not. New cells, coming from the bone marrow, broke the tolerant state within a month. When TD cells were present both populations of BMD cells, as well as the TD cells, were made tolerant. New BMD cells regenerating from the bone marrow abrogated the tolerant state of the BMD population. This breaking of tolerance could only be seen in mice given additional thymocytes as the tolerance of the TD cells was not broken in the absence of a thymus. Thus, the induction of tolerance as well as the induction of immunity in thymus dependent BMD cell populations, seems to require the co-operation of TD cells. [ABSTRACT FROM AUTHOR]