bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of PGE on the immune response in melanoma-bearing mice.
Authors: Favalli C , Garaci E , Etheredge E , Santoro M G , Jaffe B M
Published: December 2022

This study was performed to correlate the role of exogenous and endogenous prostaglandins on humoral and cellular immune responses to and rate of growth of B-16 melanoma in vivo. B-16 melanomas synthesized 7 times as much PGE as did adjacent normal tissues, an effect that was abolished by indomethacin. In C57BL/6J mice bearing B-16 melanomas splenic plaque-forming cells, hemagglutinin titers, and delayed hypersensitivity (all to SRBC) were profoundly suppressed; these responses were significantly augmented by treating the mice with di-M-PGE2 (16, 16-dimethyl-PGE2-methyl ester), a long acting analogue of PGE2, and either further suppressed or unaffected by indomethacin, a potent inhibitor of endogenous PGE biosynthesis. Compared to control experiments, indomethacin hastened the rate of development of palpable subcutaneous B-16 tumors and facilitated the proliferation of these cells in solid tumors as well as in ascites. Pretreatment of mice with di-M-PGE2 (before inoculation with tumor cells) resulted in delay in the rate of appearance of tumors, decline in the growth rate, and increased survival. These data suggest that prostaglandins are involved in the control of in vivo tumor cell growth largely by virtue of their effects on the immune response.
Male determined accelerated autoimmune disease in BXSB mice: transfer by bone marrow and spleen cells.
Authors: Eisenberg R A , Izui S , McConahey P J , Hang L , Peters C J , Theofilopoulos A N , Dixon F J
Published: December 2022

Autoimmune disease in BXSB mice progresses more rapidly in male animals. We have investigated the cellular basis of this effect by transferring male and female bone marrow and spleen cells into male and female lethally irradiated BXSB recipients. The rate of development of disease was measured by the overall mortality rate, mortality from glomerulonephritis, and development of serologic abnormalities. We found that the pace of disease in the BXSB sex chimeras was determined entirely by the sex of the donor of the transferred cells. Lethally irradiated BXSB animals receiving male cells had rapidly progressive disease, whether the recipients were themselves male or female, whereas female-cell recipients of either sex had slowly progressive disease. The male-specific effect that accelerates autoimmune disease in the BXSB is thus not hormonally mediated, but rather is expressed in the hematopoietic stem cell populations.
The cellular basis for viral-induced immunodeficiency: analysis by monoclonal antibodies.
Authors: Reinherz E L , O'Brien C , Rosenthal P , Schlossman S F
Published: December 2022

Viral infections are often associated with immunodeficiency states. Although T lymphocytes have been thought to suppress the host's response, the precise etiology remains unclear. Therefore, we characterized T lymphocytes from six patients during both acute and convalescent phases of infectious mononucleosis (IM) with monoclonal antibodies (titer, 10(-5) to 10(-7) to antigens restricted to the TH2- helper (T4) and TH2 suppressor (T5) T cell subsets as well as to a common T cell antigen (T3) and HLA-D related Ia antigens. It was found that during acute infectious mononucleosis, there is both activation and increase of suppressor T cells (T5+, Ia+ phenotype). Fuctionally, the acute IM lymphocytes suppress autologous T cell proliferation to antigens as well as pokeweed mitogen driven B cell immunoglobulin production. In contrast, convalescence is associated with a return to normal of T cell subsets and immune function. These results demonstrate that viral infections can preferentially activate a specific T cell subset and suppress the overall human immune response.
Genetic control of cytolytic T lymphocyte responses. III. The role of K and I region alleles on the specificity of the cytolytic T lymphocyte response to trinitrophenyl-modified syngeneic cells.
Authors: Burakoff S J , Riccio J , Billings P , Benacerraf B , Dorf M E
Published: December 2022

It has previously been demonstrated that genes in the H-2K and/or I-A region control the specificity of the cytolytic T lymphocyte (CTL) response to trinitrophenyl-(TNP) modified syngeneic cells. Strains of mice bearing the k allele in the K and/or IA region do not exhibit cross-reactive lysis of TNP-modified allogeneic targets after stimulation with TNP-modified syngeneic targets. In this report we present evidence for independent roles of genes in the H-2K and I-A regions on the control of CTL specificity. One gene, mapping in the H-2K region, is expressed on the stimulator cell population, whereas the other gene maps to the I region and is expressed in the population of responding cells and need not be expressed in the stimulator cell population. Thus, we suggest that Ir genes localized to the I region may influence the response for prekiller cells to H-2K/D gene products.
Regulatory role of IgE-binding factors from rat T lymphocytes. II. Glycoprotein nature and source of IgE-potentiating factor.
Authors: Yodoi J , Hirashima M , Ishizaka K
Published: December 2022

Previous experiments have shown that Fc epsilon receptor-bearing (Fc epsilon R(+)) T lymphocytes in mesenteric lymph nodes (MLN) of rats infected with Nippostrongylus brasiliensis (Nb) release a soluble factor that selectively potentiates the IgE response. The IgE-potentiating factor has affinity for IgE, and can be detected by the ability to inhibit rosette formation of Fc epsilon R(+) cells with IgE-coated erythrocytes. The factor was bound to IgE-coated Sepharose and was eluted from the beads at acid pH. It was also found that the IgE-potentiating factor binds to lentil lectin-Sepharose, indicating that the factor is a glycoprotein. The affinity of the factor for IgE was lost after treatment with trypsin but was maintained after treatment with neuraminidase. However, the ability of the factor to potentiate the IgE response was lost after neuraminidase treatment. The results suggested that the factor's binding site for IgE is associated with a protein (peptide) moiety but that its carbohydrate moiety is essential for its biologic activity. When MLN cells were incubated at 37 degrees C, a substantial amount of the IgE-potentiating factor was released into culture medium within 4 hr even in the presence of cycloheximide. Pretreatment of the cells with trypsin, which removed Fc epsilon R, markedly diminished the release of IgE-potentiating factor, suggesting that the factor is derived from Fc epsilon R on the cell surface.
Antigen recognition by T cells. II. Intravenous administration of native or denatured ovalbumin results in tolerance to both forms of the antigen.
Authors: Endres R O , Grey H M
Published: December 2022

In the accompanying report, suppressor T cells were demonstrated that did not recognize cross-reactivity between native and denatured ovalbumin (N-OVA and D-OVA). Here we show that the T cell tolerance induced by i.v. injections of antigen does detect cross-reactivity between N-OVA and D-OVA. Mice that had been immunized with either N-OVA or D-OVA in adjuvant could be rendered profoundly unresponsive if either N-OVA or D-OVA, but not an unrelated protein, were injected i.v. Cross-tolerance was observed in assays of antigen-induced T cell proliferation and helper T cell activity. Tolerance was distinguished from suppressor T cell activity by three criteria: 1) specificity for N-OVA and D-OVA, 2) sensitivity to abrogation by cyclophosphamide, 3) duration of effectiveness. These results confirm observations made by others that suggest that tolerance is mediated by an additional mechanism(s) other than suppressor T cells. Based on a hypothesis that cross-reactivity between native and denatured antigen is related to macrophage processing of antigen, these data also suggest a critical role for processed antigen in the induction of tolerance when antigen is administered i.v.
A comparative analysis of the cell surface properties of activated vs endogenous mouse natural killer cells.
Authors: Kiessling R , Eriksson E , Hallenbeck L A , Welsh R M
Published: December 2022

Mouse natural killer (NK) cells can be activated by interferon and by interferon inducers, such as viruses. In the present report we compared the cell surface properties of the nonactivated "endogenous" NK cells from normal mice with NK cells activated in vivo by acute infection with lymphocytic choriomeningitis virus (LCMV) or in vitro by interferon. Several striking differences were found: 1) in vivo LCMV-activated as well as in vitro interferon-activated NK cells were more adherent to nylon wool columns than the endogenous NK cells; 2) activated NK cells were more EA-monolayer adherent than endogenous NK cells; this adherence could be blocked by streptococcal A protein, indicating that activated NK cells expressed greater Fc receptor mediated adherence; 3) LCMV-activated NK cells that passed through nylon wool columns expressed relatively low EA adherence properties; 4) the sensitivity of NK cells to anti-theta serum + complement treatment was increased in spleen cells late after LCMV infection (day 6 to 7) but not in spleen cells early after infection (day 2 to 3); 5) as shown by centrifugal elutriation, LCMV-activated spleens contained a population of large NK cells that were not present among endogenous spleen cells. In contrast to previous reports, these findings show that there are several distinct changes as a result of both long-term in vivo activation or of short-term in vitro activation of NK cells. These changes might functionally be involved in the increased lytic ability of activated NK cells.
Immunologic abnormalities in HRS/J mice. I. Specific deficit in T lymphocyte helper function in a mutant mouse.
Authors: Morrissey P J , Parkinson D R , Schwartz R S , Waksal S D
Published: December 2022

An immunologic analysis of mutants HRS/J mice was done comparing hr/hr homozygotes to hr/+ heterozygotes. It was shown that hr/hr spleen but not lymph node cells show a defect specific for functions associated with T helper cells as compared to hr/+ littermates. This defect, which is expressed by depressed proliferative responses to alloantigens, does not affect the ability of hr/hr spleen cells to respond normally to T cell mitogens nor does it affect their ability to generate normal cytotoxic effector cells in vitro. It is further suggested that this defect is due to an abnormality in thymus epithelium, which is also related to the high grade expression of xenotropic virus in old hr/hr thymocytes and subsequent development of leukemia.
Monoclonal antibodies to murine cell surface antigens. I. Lyt-1.1.
Authors: Hogarth P M , Potter T A , Cornell F N , McLachlan R , McKenzie I F
Published: December 2022

The production and properties of a monoclonal anti-Lyt-1.1 antibody are described. The monoclonal antibody is of the IgG2a subclass, is cytotoxic, and reacts with Staphylococcal protein A. The tissue culture supernatant has the same activity (titer on thymus > 1/1000) as an anti-Lyt-1.1 produced by a standard immunization procedure, and after in vivo passage of the hybridoma cell line, the serum titer was > 1:10(6). The monoclonal antibody has the same strain and tissue distribution as the conventional antibody, including reactions on Lyt-1 congenic strains, and it precipitates a cell surface molecule of m.w. approximately 67,000. In nonprimed mice, there were similar numbers of Thy-1+ and Lyt-1+ cells in spleen, lymph node, and thymus. By using the monoclonal reagent, T-helper and T-killer cells in an allogenic system were shown to be Lyt-1.1.
Delayed hypersensitivity to crude and partially purified murine tumor-specific transplantation antigens and alloantigens utilizing the footpad swelling assay.
Authors: Macek C M , Kahan B D , Pellis N R
Published: December 2022

Antigen preparations extracted from C3H/HeJ methylcholanthrene-induced fibrosarcomas by the 3M KCl extraction procedure were assessed for tumor-specific and allospecific antigenicity. Specificity of crude tumor antigen preparations and of fractions from preparative isoelectric focusing was investigated by evocation of footpad swelling (FPS) in syngeneic mice immunized with irradiated fibrosarcoma cells. Tumor immune mice displayed delayed hypersensitivity as positive FPS responses to challenge with 3M KCl extract and with fraction (Fr) 15 (pH 5.7 to 6.0) from preparative isoelectrically focused 3M KCl extract. Crude extracts and Fr 15 exhibited immunoprotective activity in vivo. Immune mice demonstrated a specific FPS response only to crude antigen preparations of Fr 15 from immunizing tumors, not to materials from a noncross-reactive neoplasm. DBA/2J mice immunized with C3H/HeJ spleen cells displayed FPS to challenge with crude antigen preparations, but not with the tumor-specific Fr 15. Alloantigen activity, however, was detected by a positive FPS response in C3H-immune DBA mice in fractions from the pH range 5.1 to 5.5. These experiments demonstrated that the FPS assay provides the setting for detection of specific delayed hypersensitivity responses to crude and fractionated tumor antigen preparations and for delineation of tumor-specific and histocompatibility antigen activities in fractions from crude extracts.
Macrophage accumulation in murine ascites tumors. I. Cytoxan-induced dominance of macrophages over tumor cells and the anti-tumor effect of endotoxin.
Authors: Dye E S , North R J
Published: December 2022

The host cellular response to i.p. growth of the SA-1 spindle cell sarcoma was studied in semisyngeneic AB6F1 hybrid mice. At progressive stages of tumor growth mice were sacrificed, their ascites were collected, and changes in the numbers of tumor cells, macrophages, lymphocytes, and granulocytes were determined. It was found that macrophages were the predominant host cell that accumulated locally in response to tumor growth. Cytoxan treatment caused a 90% reduction in tumor cells without affecting the accumulation of macrophages. Six days after treatment with cytoxan, macrophages exceeded all other cell types present in the peritoneal cavity and outnumbered tumor cells by 20:1. However, in spite of this macrophage dominance, the tumor cells ultimately regrew to kill the host. Ascites tumors could be completely regressed, however, by following cytoxan treatment ith an appropriately timed intratumor injecton of endotoxin. The relatively long delay before endotoxin caused the tumor to regress suggests that endotoxin acted by stimulating the generation of anti-tumor immunity, rather than by directly augmenting the tumoricidal activity of macrophages.
Alterations in cyclic nucleotides and cyclase-specific activities in T lymphocytes of aging normal humans and patients with Down's syndrome.
Authors: Tam C F , Walford R L
Published: December 2022

The levels of cyclic adenosine 3'5'-monophosphate (cAMP) in unstimulated (resting) peripheral blood thymus-derived lymphocytes (T cells) from normal old humans and young-adult Down's syndrome (DS) patients were markedly decreased when compared with those of young normal humans. By contrast, the cyclic guanosine 3'5'-monophosphate (cGMP) in resting T cells from normal old and young-adult DS patients were greatly increased. The cAMP/cGMP ratios for unstimulated T cells therefore declined in normal aged and DS subjects. The specific activity of adenylate cyclase (ATP pyrophosphate-lyase[cycling]E.C.4.6.1.1) was elevated in T cells from the aged and DS groups, whereas that of guanylate cyclase (GTP pyrophosphate-lyase[cycling]E.C.4.6.1.2) decreased with age and in DS. These results denote the existence of substantial age-related biochemical changes in peripheral T cells. An imbalance in resting cyclic nucleotide levels and their generating enzymes in T cells of normal aging and DS subjects might contribute to the immune dysfunction occurring both with aging and in DS.
Development of B lymphocytes in the mouse; studies of the frequency and distribution of surface IgM and IgD in normal and immune-defective CBA/N F1 mice.
Authors: Scher I , Berning A K , Kessler S , Finkelman F D
Published: December 2022

Affinity-purified anti-mouse mu and delta antibodies and flow microfluorometric techniques were utilized to study the frequency and distribution of sIgM and sIgD on adult and neonatal B lymphocytes of immunologically normal mice and mice with the immune-defect characteristic of the CBA/N strain. Neonatal normal B lymphocytes can be distinguished from their adult counterparts by the presence of increased amounts of sIgM on sIgM+ cells and by the increased number of sIgM+IgD- cells. The most primitive B lymphocytes of immunologically normal mice appear to reside in the bone marrow of 1- to 2-wk-old mice and are distinguished from splenic B lymphocytes at this time by their relatively low amounts of sIgM. However, in the adult, splenic and bone marrow B lymphocytes are indistinguishable with regard to the quantities of their sIgM or sIgD. Adult immune-defective mice have increased amounts of sIgM on their B lymphocytes, although the number of sIgM+ IgD- cells in these mice is not increased. During development, however, larger than normal numbers of sIgM+ IgD- cells are found in the spleen and bone marrow of these mice; and the low frequency of such cells seen in normal adults is not achieved in immune defectives until after the 56th day of life. Thereafter, immune-defective mice have low frequencies of B lymphocytes with high relative amounts of sIgM, even after 1 yr or age.
Cell-mediated immunity in interstitial nephritis. III. T lymphocyte-mediated fibroblast proliferation and collagen synthesis: an immune mechanism for renal fibrogenesis.
Authors: Neilson E G , Jimenez S A , Phillips S M
Published: December 2022

Fibroblast proliferation and collagen synthesis play an important role in the progression of intersititial nephritis. To evaluate the involvement of immune mechanisms in this process, we induced intersititial nephritis in guinea pigs utilizing injections of tubular antigens. Over a 3-week period, injected animals developed a nephritis characterized by mononuclear infiltrates and expanding areas of fibrotic scar formation. Involved kidneys contained increased collagen as compared to controls. To identify mediators of the observed fibrogenesis, T lymphocytes from nephritic and control animals were stimulated with soluble tubular antigens. Dialyzed supernatants from control lymphocyte cultures contained an inhibitor of both fibroblast proliferation and collagen synthesis. In contrast, supernatants from nephritic animals demonstrated absence of inhibition and a progressively increasing titer of a factor that enhanced both kidney fibroblast proliferation and collagen synthesis. As the disease progressed, however, nephritic lymphocytes also began secreting an inhibitor of proliferation that could be detected in low levels. These studies suggest, therefore, that immune mechanisms and altered lymphocyte function may play an important role in the development, progression, and regulation of renal fibrogenesis in intersititial nephritis.
Developmental profile of chicken splenic lymphocyte responsiveness to Con A and PHA and studies on chicken splenic and bone marrow cells capable of inhibiting mitogen-stimulated blastogenic responses of adult splenic lymphocytes.
Authors: Kline K , Sanders B G
Published: December 2022

Embryonic and newly hatched chicken splenic lymphocytes were analyzed for their ability to respond to 2 mitogens, Con A and PHA. Acquisitions of the ability to respond to both mitogens began at hatch and responses to both mitogens reached normal adult blastogenic response levels by 11 days post-hatch. Splenic lymphocytes in the developing embryo and newly hatched chicken were found to be capable of inhibiting the Con A- and PHA-mediated blastogenic responses of both syngeneic and allogeneic adult splenic lymphocytes. The ability to suppress adult responses was first observed on E12, reached a maximum of suppressive ability on E18, and the suppressive ability was gradually lost with development such that no suppressive ability was exhibited after H11. Ability to suppress adult splenic lymphocyte proliferation to mitogens was found to not be a unique property of splenic lymphocytes but was also exhibited by bone marrow cells. The ability of bone marrow cells to suppress adult splenic lymphocyte proliferation to Con A and PHA gradually decreased with chicken aging but the suppressive ability was never lost and adult bone marrow cells were found to exhibit significant degrees of suppressive ability. The mechanism of suppression by the 1-day-hatched splenic lymphocytes was found to be cell-to-cell contact mediated and did not require any newly synthesized H1 splenic products, since x-ray killed cells were able to suppress as well as live cells.
Direct demonstration of specific suppressor T cells in the mice tolerant to type III pneumococcal polysaccharide: two-step requirement for development of detectable suppressor cells.
Authors: Braley-Mullen H
Published: December 2022

Spleen cells from CAF1 mice made tolerant to type III pneumococcal polysaccharide (S3) with S3 coupled to syngeneic spleen cells (S3-SC) develop S3-specific suppressor T cells (Ts). These Ts could be demonstrated consistently only when spleen cells from tolerant mice were cultured in vitro with the specific antigen and the specific tolerogen. Spleen cells from normal mice cultured under the same conditions did not suppress the antibody response to S3. When different numbers of Ts were transferred to normal CAF1 mice, an unusual dose-effect pattern was observed. Maximal suppression of the S3 response occurred when relatively low numbers of Ts, 3 to 30 x 10(5) per recipient, were transferred, whereas larger numbers of cells, 150 x 10(5) per recipient, were not suppressive. These results indicate that a presumably T-independent antigen, S3, can activate antigen-specific Ts. These Ts exhibit unusual dose effects upon transfer and require both an in vivo induction period and in vitro activation for development of maximal activity. These latter observations suggest that S3 may activate a different population of T cells with suppressor function than do conventional T-dependent antigens. The loss of suppression observed when greater than optimal numbers of cells were transferred suggests that a second type of T cell, which has the ability to 'neutralize' the activity of S3-specific Ts, is also induced in the same spleen cell population.
Characterization of mouse helper and suppressor T cell subsets separated by lectins.
Authors: Nakano T , Imai Y , Naiki M , Osawa T
Published: December 2022

Concanavalin A (Con A)-activated cells were fractionated by separating cells that agglutinate with peanut agglutinin (PNA) which binds preferentially to the sugar sequence beta-D-Gal-(1 leads to 3)-D-GalNAc. PNA-agglutinable cells were found to exert a significant suppressor effect on the primary antibody response to sheep red blood cells, whereas PNA-nonagglutinable cells did not affect the antibody response. It was also found that PNA-agglutinable suppressor cells were sensitive to treatment with anti-Thy 1.2 and complement (C), anti-I-J antiserum and complement, and anti-Ly 2.2 antiserum and complement. These results suggest that the PNA-agglutinable suppressor cells, separated from Con A-activated cells, were T cells and that these suppressor T cells possess abundant beta-galactosyl residues exposed on the cell surface, not masked by sialyl residues. Furthermore, it was found that antigen-specific suppressor cells were also separable by use of the agglutinability with PNA. The PNA-agglutinable suppressor T cell activity was eliminated by treatment of the Con A-activated PNA-agglutinable cells with anti-asialo GM1 and complement, anti-Forssman antiserum and complement, and anti-globoside antiserum and complement, but not by treatment with anti-GM1 antiserum and complement. Conversely, the helper T cell activity that was induced by Lens culinalis agglutinin and separated by Limulus polyphemus agglutinin, was eliminated by treatment of the cells with anti-GM1 and complement, but not by the treatment with the other anti-glycolipid antisera and complement.
The use of a clonal assay for cytotoxic T lymphocytes to determine the Ly phenotypes of the cytotoxic precursor and effector cells to alloantigens and trinitrophenyl-modified self antigens.
Authors: Teh H S , Teh S J
Published: December 2022

Considerable controversy has arisen regarding the Ly phenotypes of cytotoxic T lymphocytes (CTL) and their precursors (CLP) to alloantigens and modified-self antigens. Although there is general agreement that all CTL and their pregenitors express the Ly2 alloantigen, the presence of the LY1 alloantigen on either CTL or CLP is debated. Clonal assays for CLP, capable of detecting single CLP in the absence of accessory cells, have recently been developed. This assay system provides a sensitive means of determining the Ly phenotypes of CLP to alloantigens or trinitrophenyl- (TNP) modified self antigens. Lymph node cells from C57BL/6 (Ly-1.2, 2.2, 3.2) or CBA (Ly-1.1, 2.1, 3.2) mice were treated with anti-Ly serum and complement (C), and the frequencies of CLP of the treated populations to alloantigens or TNP-modified self antigens were determined. We found that the number of CLP reactive to alloantigens or TNP-modified self antigens were greatly reduced after treatment with either anti-Ly-1 or anti-Ly-2 serum and C in both C57BL/6 and CBA mice. In other words, the CLP to alloantigens or TNP-modified self antigens in these 2 strains of mice are Ly 1+2+. We also found that the CTL derived from the Ly1+2+ CLP were also Ly1+2+. The significance of this finding with respect to the cytotoxic repertoire for alloantigens and modified self antigens is discussed.
Different stimulating capacity of B and T lymphocytes in primary and secondary allogeneic reactions: cellular detection of HLA-D products on T lymphocytes.
Authors: Wollman E E , Cohen D , Fradelizi D , Sasportes M , Dausset J
Published: December 2022

The present study was undertaken to define the best way to produce and to test primed lymphocyte typing (PLT) cells using B- and T-enriched lymphocyte suspensions. Intrafamilial PLT cells were produced with primed unseparated and T purified lymphocytes against haplo-identical donors' T and B cells. These PLT cells were then restimulated with a panel of related or unrelated individuals' T and B cells and with allogeneic in vitro activated T cells. The best discrimination was obtained when PLT reagents, regardless of the production method, were restimulated by a B-enriched population of peripheral lymphocytes. Furthermore, the results have shown that enriched primed or unprimed T cell suspensions stimulated by enriched T lymphocytes did not give any proliferation. Experiments performed to explain the results led us to distinguish 2 different phenomena: in primary cultures, the addition of monocytes autologous to the responder cell restored the proliferation of enriched T cells stimulated by T lymphocytes. In secondary cultures, the addition of monocytes autologous to the PLT cell did not restore the proliferation of PLT lymphocytes stimulated by enriched T cells. This was shown to be due to the lack of Dr antigen on the stimulating cell: if allogeneically activated T cells were used as stimulating lymphocytes, a DR-specific proliferative response appeared. This correlates with serologic findings were DR determinants are found on activated T cells and not on unprimed T lymphocytes. However, this difference might be only quantitative, since peripheral lymphocytes could be primed by T cells and be DR specifically restimulated.
Ly 9, an alloantigenic marker of lymphocyte differentiation.
Authors: Mathieson B J , Sharrow S O , Bottomly K , Fowlkes B J
Published: December 2022

A new lymphocyte cell surface alloantigen, provisionally designated Ly 9, is detected by flow microfluorometry(FMF), as an extra specificity in sera from anti-Lyt immunizations. Ly 9.2, one of the allelic specificities, commonly is detected as a unique immunofluorescence profile of thymocytes with anti-Lyt 3.1 sera. The alternative antigenic specificity, Ly 9.1, can be detected routinely in antisera prepared against Lyt 2.1 and Lyt 3.2. This lymphocyte alloantigen has both a unique strain and cell/tissue distribution. Quantitative measurement of Ly 9 immunofluorescence by FMF on heterozygote cells shows that Ly 9 antigen expression is co-dominant and reduced in levels relative to parental homozygote cells. Ly 9 is expressed on all thymocytes, peripheral lymphocytes, and on a subpopulation of cells in the bone marrow. This antigen is not expressed to any significant degree on erythrocytes, epidermal cells, sperm, or in suspensions of testis, brain, kidney, liver, or lung. FMF analysis and absorption typing reveals a quantitatively lower level of antigen expression on thymocytes compared with spleen or lymph node cells. Cytotoxic elimination experiments confirm that Ly 9 is expressed on at least 2 different T cell functional subsets and B cells.
A monoclonal antibody (TA-1) reactive with human T lymphocytes and monocytes.
Authors: LeBien T W , Kersey J H
Published: December 2022

Several monoclonal antibodies were produced against the human T lymphocyte leukemia cell line HSB-2 by fusing spleen cells from hyperimmune mice with NS-1 myeloma cells. One clone, designated TA-1, was initially characterized for reactivity with normal and leukemic human hematopoietic cells. Using indirect immunofluorescence, TA-1 was shown to bind to approximately 75% of peripheral blood lymphocytes. Enrichment for T and B lymphocytes followed by double fluorochrome labeling studies revealed that most if not all E+ T lymphocytes and approximately 10% of B lymphocytes were TA-1+. TA-1 also reacted with approximately 67% of thymocytes, mixed lymphocyte culture-activated T lymphocytes, the entire peripheral blood monocyte population, and approximately 13% of nucleated bone marrow cells. TA-1+ cells in bone marrow included both phagocytic and nonphagocytic cells. TA-1 did not bind to peripheral blood granulocytes, red blood cells, or platelets. Studies of acute lymphoblastic leukemia (ALL) revealed that 6 of 11 T-ALL and 1 of 21 E-, SIg--ALL were TA-1+, whereas cells from 10 patients with chronic lymphocytic leukemia were TA-1-. Interestingly, TA-1 was able to distinguish acute myelomonocytic leukemic cells (TA-1+) from acute myelocytic leukemic cells (TA-1-). In summary, these studies demonstrate the existence of determinant recognized by TA-1 that is primarily expressed on cells of T lymphocyte and monocyte/macrophage lineage.
Cell-mediated immunity to non-HLA antigens of the host by donor lymphocytes in patients with chronic graft-vs-host disease.
Authors: Tsoi M S , Storb R , Dobbs S , Medill L , Thomas E D
Published: December 2022

Forty-four patients with aplastic anemia or leukemia were given marrow grafts from siblings selected on the basis of HLA-A and -B identity and mutual nonreactivity of their lymphocytes in mixed leukocyte culture (MLC). Twenty-two to 1089 days after grafting, their lymphocytes (of donor origin) were tested for reactivity in MLC to lymphocytes from the host (cryopreserved before grafting), the marrow donor, and unrelated individuals. Lymphocytes from 14 of 22 long-term survivors with chronic graft-vs-host disease (GVHD) showed unidirectional reactivity in response to host lymphocytes manifested as high stimulation indices (SI) and high relative responses (RR). Lymphocytes from only 1 of 12 long-term survivors without chronic GVHD showed unidirectional reactivity to host lymphocytes. Statistical analysis showed that lymphocytes from patients with chronic GVHD displayed anti-host responses that were significantly higher than those of lymphocytes from either marrow donors (p < 0.001) or patients without GVHD (p = 0.03). Lymphocytes from 5 patients with and 5 without acute GVHD, tested shortly after marrow grafting, failed to show responses to host cells. The results are consistent with a participation of cell-mediated immunity of graft against host in chronic GVHD.
Evidence for the cellular origin of Gross virus-induced leukemia in the rat: description of a unique LDH isozyme sub-band in leukemic lymphoid cells and lymphohemopoietic precursor cells.
Authors: Barton R W , Tausche F , Goldschneider I
Published: December 2022

Neoplastic thymocytes from rat thymic lymphoma-leukemias induced by the rat-adapted Gross-leukemia virus (RAGV) were analyzed for a variety of differentiation markers to define their differentiation state and possible cellular origin. A majority of thymocytes from leukemic rats had the phenotypic characteristics of subcapsular cortical thymocytes that are the most ancestral of the thymocytes. These cells exhibited readily detectable levels of Thy-1 and histocompatibility antigens on their surfaces, they contained terminal deoxynucleotidyl transferase (TdT) and they contained low adenosine deaminase (ADA) and high purine nucleoside phosphorylase (PNP) specific activity. The leukemic thymocytes also contained a sub-band of the LDH-5 isozyme (LDH-5') that was not detected in normal thymocytes but that was present in lymphocyte-rich fractions of postnatal bone marrow, fetal and prepubertal spleen, and fetal and neonatal liver. The tissue distribution and ontogeny of LDH-5'-containing cells is similar to prethymic TdT+ cells in the rat and both TdT and LDH-5' are enriched in a subset of bone marrow "null" cells. These results suggest that TdT+ thymocyte progenitors or their precursors are the targets of leukemic transformation of RAGV.
Selective depletion of human natural killer cells on monolayers of target cells.
Authors: Phillips W H , Ortaldo J R , Herberman R B
Published: December 2022

The specificity of human natural killer (NK) cells recently has been evaluated by examining direct cytotoxic reactions against a variety of target cells and by cold target inhibition assays. Although these studies have provided evidence for the multiplicity of NK antigens, they did not indicate whether NK cells were heterogeneous, with subpopulations recognizing different specificities. We have examined this issue by using a tumor cell-monolayer adsorption technique that allowed the removal of NK-reactive cells by adsorption to monolayers of various NK-sensitive target cells. After depletion of cells capable of binding to a particular monolayer, the remaining cells were tested for cytotoxicity against a panel of 5 target cells. With several donors, the monolayers were effective in depleting most or all reactivity against the same target cell but only removed a portion of reactivity against some other target cells. The patterns of reactivity after adsorption, although varying among the donors, were consistent upon repeat testing of the same donor. To account for the reactivities of the various donors that remained after adsorption, it was necessary to postulate at least 7 antigenic specificities. These results indicate that human NK cells may be heterogeneous, with each subpopulation recognizing different antigenic specificities on target cells.
Cell surface DNA in immunosuppression in AKR leukemia.
Authors: Russell J L , Golub E S
Published: December 2022

Spleen cells from leukemic AKR mice contain nonspecific T suppressor cells that suppress the in vitro anti-SRBC responses of normal AKR spleen cells. The suppression is abrogated by pretreatment of the leukemic cells with DNase. Cells with surface DNA can be enriched by treatment with anti-DNA antibodies and removed on anti-Ig columns. Even though there is a 10-fold enrichment in suppression by the surface DNA-positive cells (DNA+), the depleted population (DNA-) still suppresses with an efficiency comparable to the unfractionated spleen cells. Pretreatment with anti-I-J antiserum and separation on columns neither enriches nor depletes suppressor cells. Fractionating leukemic spleen into 4 populations of cells by sequential treatment with anti-DNA and anti-I-J with separation on appropriate columns, resulting in 4 populations (DNA+/I-J-, DNA+/I-J+, DNA-/I-J+, and DNA-/K-J-), revealed that the DNA+/I-J- cells that comprise ca. 15% of the total are the most potent suppressors. The DNA+/I-J+ cells that comprise ca. 2% of the cells are less efficient and their suppression is not sensitive to DNase. The DNA-/I-J+ population (ca. 10% of the total) are also poor suppressors. The remaining cells, which are DNA-/I-J-, do not act as suppressors. When small numbers of any 2 of the 4 fractions were added together, it was found that the DNA+/I-J- cell can interact with the DNA+/I-J+ and the DNA-/I-J+ cells but not the DNA-/I-J- cells to give enhanced suppression.
T lymphocytes in colostrum and peripheral blood differ in their capacity to form thermostable E-rosettes.
Authors: Richie E R , Steinmetz K D , Meistrich M L , Ramirez I , Hilliard J K
Published: December 2022

The cellular population of human breast milk collected within 5 days postpartum consists primarily of lipid laden polymorphonuclear leukocytes and macrophages, whereas lymphocytes comprise < 10% of the total cells. A discontinuous density gradient technique was developed to obtain highly enriched (75 +/- 6%) fractions of milk lymphocytes. The majority of milk lymphocytes are T cells as determined by their capacity to form rosettes at 4 degrees C with sheep erythrocytes (E). The lymphocytic origin of the rosetted cells was confirmed by morphologic evaluation of Wright-Giemsa-stained cytocentrifuge slides. A novel finding is that a large proportion of milk T lymphocytes form E-rosettes at 37 degrees C as well as at 4 degrees C. The capacity to form thermostable E-rosettes is not a general property of T lymphocytes in the postpartum period, since peripheral blood T lymphocytes from milk donors form few thermostable E-rosettes. In addition, peripheral blood lymphocytes did not acquire the capacity to form thermostable E-rosettes after density gradient centrifugation nor after incubation with autologous milk. The finding that T lymphocytes in milk form thermostable E-rosettes suggests that milk T lymphocytes may be activated or immature. In either case, these data support the concept that lymphocytes that home to the mammary gland are a select subset of the total lymphocyte population.
Role of self carriers in the immune response and tolerance. VI. Induction and reversal of TNP-modified self unresponsiveness in vitro.
Authors: Li J T , Scott D W
Published: December 2022

The involvement of T-suppressor cells in hapten-modified self unresponsiveness induced in vivo is well established. However, TNP-modified syngeneic spleen cells (TNP-SC) can block the anti-TNP PFC response of normal or nude spleen cells to TNP-immunogen in vitro, an effect that is apparently T cell-independent. In this study, we have used a 2-stage culture system in which both the induction of tolerance by irradiated syngeneic TNP-SC and the subsequent challenge with TNP-immunogen take place in vitro to dissect the cellular events that lead to unresponsiveness. Our results show that not only are spleen cells precultured with TNP-SC tolerant to challenge, but that these cells are able to specifically suppress the response of freshly prepared normal spleen cells to the T-independent antigens TNP-POL or TNP-LPS. Irradiation of the precultured cells abrogates the suppressor activity and rules out hapten carryover as the mechanism of suppression. Suppressor cells were able to inhibit the response of anti-Ba theta and C-treated spleen cells, suggesting that suppressor function is directed toward the B cell and/or accessory cells. Anti-Ba theta and C treatment of spleen cells before preculture with TNP-SC prevented the induction of both tolerance and suppression. Nylon wool-enriched T cells, on the other hand, could generate suppressor cells in response to TNP-SC. These results demonstrate that, like the in vivo situation, T cells are involved in the generation of this form of B cell tolerance in vitro. Implications relevant to the mechanisms of tolerance induction are discussed.
Hapten-specific T cell response to azobenzenearsonate-N-acetyl-L-tyrosine in the Lewis rat. I. Induction and suppression of delayed-type hypersensitivity and in vitro proliferative responses.
Authors: Lawn C Y , Leskowitz S
Published: December 2022

Pretreatment of Lewis rats with a single i.p. injection of ABA-N-acetyl-tyrosine in incomplete Freund's adjuvant induced an unresponsiveness for delayed-type hypersensitivity to subsequent immunization with the same antigen in complete Freund's adjuvant. Complete suppression of in vitro antigen-induced proliferative responses required repeated pretreatment. Passive transfer of lymphoid cells from spleen and lymph nodes but not sera from suppressed rats induced unresponsiveness of hapten-specific T cell functions. Nylon wool-nonadherent cells and cells panned on F(ab')2 of rabbit anti-Lewis rat Ig plates suppressed the induction of DTH and in vitro antigen-stimulated proliferation. Adult thymectomy increased DTH and failed to abolish the induction of suppression.
Generation of H-2-restricted cytotoxic T cells by ultraviolet light-treated trinitrophenyl-modified syngeneic cells: increased requirement for adherent cells.
Authors: Hurme M , Bång B E , Sihvola M
Published: December 2022

Metabolically inactive (ultraviolet light- [UV] irradiated) cells are incapable of serving as allogeneic stimulators in a mixed lymphocyte reaction (MLR). The reason for the requirement of metabolic activity is not known. Now we have used UV-irradiated, trinitrophenyl- (TNP) coupled syngeneic spleen cells as stimulators in vitro to generate TNP-specific cytotoxic T cells (CTL). It was found that UV-irradiated cells were stimulatory only if adherent cells (nylon wool [NW] and carbonyl iron-adherent Thy-1-) were present in the responder cell population. Nonadherent allogeneic cells were also able to augment the CTL response to UV-irradiated stimulators, suggesting that the requirement for adherent cells can be replaced by the nonspecific stimulatory effects of a MLR. When spleen cells from mice primed in vivo with TNP-coupled syngeneic cells were used in vitro, it was noticed that UV-irradiated stimulators were able to induce as strong a secondary CTL response as metabolically active stimulators but this response was also entirely dependent on the presence of adherent cells in the responder cell population. As a summary, these results suggest that metabolically inactive haptenated stimulators do not present the necessary proliferative (?) stimulus to the CTL precursor cells, but this 'signal' can be mediated via the adherent cell population, thus offering an explanation for the significance of this cell type in CTL responses in vitro.
Cellular determinants of mammary cell-mediated immunity in the rat. I. The migration of radioisotopically labeled T lymphocytes.
Authors: Manning L S , Parmely M J
Published: December 2022

Current theories about the cellular basis of mammary gland immunity are based primarily on the migratory behavior of B lymphocytes bearing intracytoplasmic IgA. These B cells presumably constitute an intestinal pool that circulates independently of the peripheral B cell pool and provides a source of plasma cell precursors for secretory tissues. The hypothesis of a common, yet independent, mucosal immune system has not been applied to mammary gland cell-mediated immunity (CMI). The present study was undertaken, therefore, to compare the migration of T lymphoblasts from gut-associated mesenteric lymph nodes (MLN) with that of their counterparts recovered from cervical lymph nodes (CLN). When labeled with 3H-thymidine and adoptively transferred to lactating recipients, MLN and CLN T lymphoblasts demonstrated equal affinities for the mammary glands. This result suggests that the mammary gland can draw from both circulating pools of T cells (intestinal and peripheral). T cell migration to the mammary gland was found to increase 7- to 10-fold with the onset of lactation and remained high during the first 2 wk postpartum. Activation of MLN and CLN T cells by preculture with Con A greatly increased the proportion of large cells but not alter cell accumulation in mammary tissues. These results, discussed in the context of recent observations regarding T cell locomotion and circulating lymphocyte subsets, suggest that CMI in the mammary gland may not depend solely on oral immunization for its immunologic specificity.
Biochemical and biologic characterization of lymphocyte regulatory molecules. IV. Purification of Interleukin 2 from a murine T cell lymphoma.
Authors: Mochizuki D , Watson J , Gillis S
Published: December 2022

A cloned murine T cell line, LBRM-33 5A4, growing in culture can be activated by phytohemagglutinin (PHA) to secrete Interleukin 2 (IL-2) activity. In the absence of PHA, LBRM cells do not produce IL-2. The chemical and biologic properties of LBRM-derived IL-2 are compared to those of murine spleen-derived IL-2. The fractionation of culture supernatants from PHA-activated LBRM cells by ion-exchange chromatography, gel filtration, and isoelectric focusing (IEF) reveals that IL-2 activity is contained in a class of molecules indistinguishable in size (30,000) and charge (pI 4.3-4.7 and 4.9-5.1) from murine spleen IL-2. LBRM-derived IL-2 also exhibits the entire spectrum of biologic activities exhibited by spleen IL-2, stimulating the growth of established T cell lines in culture, the generation of cytotoxic T lymphocytes in thymocyte cultures and the induction of antibody responses in nude spleen cultures. Both LBRM and splenic-derived IL-2 activities exhibit similar properties after digestion with proteases, and various chemical and temperature treatments. Since IL-2 is derived from a cloned cell line, it is likely these lymphocyte assays are detecting a single class of molecules that act directly on activated T cells. The use of LBRM cells as a source of IL-2 should greatly facilitate studies on the molecular characterization and biologic activity of this class of lymphocyte regulatory molecules.
Functional properties of Ly 11.2 lymphocytes: a role for these cells in leukemia?
Authors: Meruelo D , Paolino A , Flieger N , Dworkin J , Offer M , Hirayama N , Ovary Z
Published: December 2022

Functional studies of lymphocyte subpopulations reveal that Ly 11.2, a newly defined T cell surface antigen, is present on prothymocytes and natural killer cells, but not on suppressor T cells for antigen-specific IgE antibody responses, Ly 1+, 2-, 3- helper T cells nor on tumor-specific cytotoxic effector cells. Changes in the expression of Ly 11.2 regularly accompany leukemogenesis and are quite distinct from changes of other cell surface antigens thus far observed. After intrathymic inoculation of radiation leukemia virus (RadLV), many more Ly 11.2-positive cells are found expressing viral antigens than cells expressing other cell surface phenotypes. In addition, after RadLV inoculation, significantly more Ly 11.2-positive cells can be found in the thymus of susceptible mice than in the thymus of resistant mice. The greater availability of permissive (Ly 11.2-positive) cells in susceptible vs resistant hosts at the time when infectious virus is present may account for the shorter latency period and high leukemia incidence of susceptible vs resistant mice.