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PubMed1988

Escape mechanisms of melanoma from immune system by soluble melanoma antigen.

We demonstrate in the B16 melanoma (C57BL/6 derived) system that the soluble form of tumor Ag preferentially suppresses immune responses 1) by inhibiting CTL activity in the effector phase and 2) by induction of specific Ts that block CTL generation in the induction phase. Soluble melanoma antigen Ag injected i.p. into the tumor-bearing host can effectively augment melanoma growth in vivo. Two T cell types with the L3T4+ or double-negative/I-J+ phenotype are involved in the suppression of anti-melanoma CTL responses and can easily be generated in the in vitro primary 12 h-culture. Anti-melanoma Ts recognizes the GM3(NeuAc) structure and distinguishes GM3 molecular species. This is because liposomes constructed with GM3(NeuAc) but not with GM3(NeuGc) gangliosides alone can effectively induce the melanoma-specific Ts. It is thus likely that tumor cells can escape from the immunologic surveillance system by stimulating the repertoire of Ts for self-Ag, GM3, which has existed even in the unprimed conditions in order to maintain self-tolerance. These would appear to be the major escape mechanisms.

Animals↗

PubMed1989

Characterization of colony-forming cells in the human thymus: evidence for a suppressor mechanism.

Activation pathways for thymic cell growth remain partially unknown. Thymocytes generally show low growth responses when cultured in the presence of mitogens, especially when T-cell colony formation by these cells is assayed. In the present work we studied the T-cell colony-forming ability of thymic subsets under phytohemagglutinin (PHA) and/or recombinant interleukin 2 (rIL2) stimulation. Our results confirm the low number of T-cell colonies obtained from human thymus as compared to bone marrow and peripheral blood sources. In contrast, significant colony numbers were observed when thymocytes were depleted of CD8+ cells. This increase was due to the suppression exerted by CD8+ cells on both CD4+- and CD4- -, CD8- -derived colony precursors. This inhibitory mechanism is dose-dependent and cannot be replaced by media conditioned by CD8+ cells. Limiting dilution analysis corroborates agar assays and points to the existence of T-cell colony-forming cells within the double-negative (CD4-, CD8-) thymic subset.

Antibodies, Monoclonal↗

PubMed1989

Immunoregulatory function of CD3+, CD4-, and CD8- T cells. Gamma delta T cell receptor-positive T cells from nude mice abrogate oral tolerance.

Previous work has shown that abrogation of oral tolerance is mediated by T cells which are found in the CD3+, L3T4- (CD4-), and Lyt-2- (CD8-) subset (termed double-negative; DN) in mice. Inasmuch as it is known that athymic, nude (nu/nu) mice possess Thy 1+, CD4-, and CD8- T cells which also exhibit a functionally rearranged TCR gamma-chain, we investigated whether this subset of nude T cells contained functional immunoregulatory cells. In this report, we examined the phenotype and distribution of CD3+ T cells in the spleen and in the mesenteric and peripheral lymph nodes of BALB/c nu/nu mice in comparison with normal mice (+/+). In the spleens of nude mice, the predominant CD3+ T cell subpopulation was DN. Further, in mesenteric and peripheral lymph nodes, approximately one-third and one-half of the CD3+ T cells were double negative, respectively. In contrast, CD3+, DN T cells represent a small subpopulation in normal (+/+) mice. We next showed that functional regulatory T cells which possess the ability to abrogate oral tolerance were induced in nu/nu mice by Ag priming. BALB/c nude mice were immunized with SRBC, and the splenic CD3+, Vicia villosa-adherent cells were obtained by panning. Adoptive transfer of CD3+, V. villosa-adherent T cells to orally tolerant BALB/c mice restored responsiveness to SRBC, whereas V. villosa nonadherent cells were without effect. In other experiments, CD3+ T cells from the spleens of SRBC-primed mice were further enriched for the CD5+, DN phenotype and adoptive transfer of this subset completely abrogated oral tolerance to SRBC. To characterize the nature of the TCR expressed on these CD3+, DN T cells, we developed a rabbit antibody to a synthetic peptide (residues 209-218: Tyr-Ala-Asn-Ser-Phe-Asn-Asn-Glu-Lys-Leu) which was synthesized from a deduced sequence of the murine delta-gene. Immunoprecipitation of a cell membrane fraction from CD3+, DN T cells with anti-delta TCR antibody isolated a 45-kDa band. Furthermore, immunoprecipitation of these cells with anti-CD3 (145-2C11) revealed bands at 45 and 35 kDa (corresponding to delta- and gamma-chains, respectively). Taken together, these results are the first to show that gamma delta-TCR bearing CD3+, CD4-, and CD8- T cells are functional and reverse oral tolerance when adoptively transferred.

Administration, Oral↗

PubMed1989

Organotin-induced thymus atrophy concerns the OX-44+ immature thymocytes. Relation to the interaction between early thymocytes and thymic epithelial cells?

After single oral application of the organotin compound di-n-butyltindichloride (DBTC) to rats, a reversible dose-dependent thymus weight reduction is observed. This is maximal at day 4 and recovers to the control value approximately at day 9 after administration. In this study the changes in thymocyte subpopulations after a single oral dose of 15 mg DBTC/kg body weight were analysed by immunohistology. Thymus glands of exposed rats were collected at day 1,2,3,4,5,7 and 9 after DBTC dosing and frozen sections were screened for various thymocyte differentiation antigens. Staining by mAb HIS-44 that labels a subset of cortical thymocytes showed that the thymus atrophy was restricted to the cortex. Here a time-dependent decrease of labelling by CD2 (OX-34), CD8 (OX-8), CD4 (ER-2), and CD5 (OX-19) was observed. In contrast, the number of cortical OX-44+ cells increased from day 2 to day 5. This increase can reflect an increase of CD4-CD8- double-negative thymocytes or of macrophages. However, most of these OX-44+ cells were negative for acid phosphatase, which is present in most macrophages. We concluded that these OX-44+ cells were mainly CD4-CD8- thymocytes and that the thymocyte subpopulation of this phenotype, i.e. CD4-CD8-OX-44+, may be the target cell for DBTC. It is discussed whether DBTC might disturb the interaction of early thymocytes and thymic epithelium, probably by an interaction with the CD2 antigen.

Animals↗

PubMed1989

Tissue localization and CD8 accessory molecule expression of T gamma delta cells in humans.

In this study, we used TCR isotype-specific antibodies to examine the frequency, phenotype, and histologic localization pattern of T gamma delta cells in humans. The TCR delta 1+ cells comprised an average of 15% of the splenic CD3+ cells and 7% of circulating T cells. The T gamma delta cells in these human tissues, like their avian counterparts, were often not "double-negative" for the CD4 and CD8 accessory molecules. Approximately 50% of the splenic delta+ cells expressed CD8, and 30% of the delta+ cells in blood were CD8+. T cells of both gamma delta and alpha beta TCR isotypes were exceedingly rare in the skin. The T gamma delta cells exhibited preferential homing to the sinusoidal areas (red pulp) of the spleen and into the epithelial layer of the intestine in humans, as had been previously noted in chickens. Although 80% of the T gamma delta cells in the human intestinal mucosa were localized in the epithelial layer, these cells represented only 5 to 10% of all the CD3+ T cells in this microenvironment. We conclude that T gamma delta cells represent a sizeable subpopulation of the T cells in human peripheral tissues. The phylogenetic conservation of the CD8 expression by peripheral T gamma delta cells and of their preferential homing pattern suggests a special role in bodily defense for this T cell subpopulation.

Aged↗

PubMed1985

Influence of cyclic AMP and hydrolysis products on cell type regulation in Dictyostelium discoideum.

We describe the effect of cyclic AMP on regulation of the proportion of prespore and prestalk cells in Dictyostelium discoideum. Prespore and prestalk cells from slugs were enriched on Percoll density gradients and allowed to regulate in suspension culture under 100% oxygen. The transition of prespore to prestalk cells is blocked by cAMP, while cAMP phosphodiesterase and caffeine cause a decrease in the number of prespore cells. This suggests that extracellular cAMP plays a role in cell type proportioning by inhibiting the conversion of prespore to prestalk cells. Low concentrations of cAMP prevent the conversion of prestalk to prespore cells; the same effect is seen with hydrolysis products of cAMP, 5 AMP, adenosine and also adenine. We suggest that, when low concentrations of cAMP are added to regulating cells, the cAMP itself is quickly broken down and the breakdown products thereafter inhibit the prestalk-to-prespore conversion. The relevance of these findings is discussed in the context of an non-positional double-negative feedback model for cell type homeostasis.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1988

Sequential events in thymocyte differentiation and thymus regeneration revealed by a combination of bromodeoxyuridine DNA labeling and antimitotic drug treatment.

The proliferative status of thymocyte cell subsets in vivo was assessed by observing the effect of two antimitotic drugs, hydroxyurea (HU) and demecolcine. Both drugs had the greatest effect on the double-positive (DP) subset followed by the L3T4+ single-positive (SP) subset. However, the decrease in the latter type was delayed by several days, showing that their precursors rather than the cells themselves were killed by HU. Double-negative (DN) cells were less affected, indicating that they contain a resting subset and that they are renewed by emigration rather than by autonomous in situ proliferation. After drug treatment all cycling cells were eliminated from the thymus but, as shown by in vivo and in vitro bromodeoxyuridine incorporation, new cells rapidly reentered in cycle, starting from DN cells and Lyt-2+ SP cells and followed by DP cells. Lyt-2+ SP cycling cells represent an intermediary stage between DN and DP cells, and they are very transient. Injection of HU 24 h after in vivo BrdUrd labeling eliminated most labeled DN cells, but did not prevent the emergence of L3T4+ SP-labeled cells on day 3 as observed in control thymuses. These results suggest that these L3T4+ SP cells are generated from DP cells in the absence of proliferation. Cycling cells in the regenerating thymus were first located at the corticomedullary junction and then in the subcapsular region, suggesting a reverse migration process to that observed after cessation of proliferation. A model is proposed to summarize these sequential events.

Animals↗

PubMed1988

Characterization of cells comprising murine thymocyte multicellular complexes.

Characterization of complexes between thymocytes and thymic stromal cells was facilitated in the present study by demonstrating that complexes would reform if cells were incubated for 1.5 to 2 h in vitro at ambient temperature. Several immunologic approaches were used to determine the phenotype of complexed cells. Bound T cells were 97% double-positive (CD4 and CD8), 3% double-negative and greater than 99% CD3 positive by using immunoperoxidase immunohistology on cytospins. Five percent expressed the TCR beta-chain and 1 to 2% were IL-2R positive. The percentages were the same whether complexes were preformed in vivo or formed in vitro. Despite the apparent absence of single positive cells in complexes, when isolated CD4 or CD8 positive cells were tested for their ability to bind to adherent thymic macrophages, each subpopulation contained some cells which were capable of complex formation. When thymocytes were fractionated by density, steroid sensitivity or peanut agglutinin positivity then allowed to form complexes, cells with an immature phenotype had a greater propensity for complex formation. Central stromal cells all were class II MHC gene product (I-A and I-E) positive, expressed macrophage-associated Ag (B23.1 and MAC-1), were negative for cytokeratin but positive for vimentin, were reactive with a polyclonal antimacrophage serum, but did not express dendritic cell Ag (33D1). The data demonstrate that immature thymocytes bind exclusively to class II MHC gene product positive thymic macrophages. This binding step may play a role in the acquisition of T cell function in the thymus.

Animals↗

PubMed1988

Thymic stroma-derived T cell growth factor: its role in the growth of immature thymocytes and T cell repertoire selection.

A newly established thymic stromal cell clone, MRL104.8a exhibited capacities to express Ia antigens and to support the growth of antigen-specific, interleukin-2 (IL-2)-dependent helper T cell (Th) clones without requirement of antigen and exogenous IL-2. Such growth was substituted by a factor produced into cultures by the MRL104.8a clone. This substance designated as thymic stroma-derived T cell growth factor (TSTGF) was demonstrated to be the protein that has an apparent molecular weight of about 25,000 and a pI of 6.0 and to be distinct from the previously described interleukins and cytokines. While the capacity of TSTGF to promote T cell proliferation was initially found by using various Th clones, further studies have demonstrated its capability of supporting the growth of immature (L3T4- Lyt-2-) thymocytes. TSTGF alone failed to function for the proliferation of double-negative thymocytes, whereas this novel growth factor was capable of inducing the proliferation of immature thymocytes by synergy with IL-1. Such growth promotion was further enhanced by the addition of IL-2 or IL-4 to cultures. The data were also presented that TSTGF could contribute to the clonal elimination in the thymus. The growth of a Th clone, 9-16, was supported on the TSTGF-producing and Ia-expressing MRL104.8a monolayer in the absence of the antigen against which this Th clone is directed. In contrast, the presence of the relevant antigen in the MRL104.8a culture elicited the lethal growth-inhibition of Th clone cells. Taken collectively, the results provide strong support for the proposition that TSTGF may play an essential role in the intrathymic T cell development in the context of T cell growth promotion and T cell repertoire selection.

Animals↗

PubMed1988

Synergistic effect of colony-stimulating factors and IL-2 on prothymocyte proliferation linked to the maturation of macrophage/dendritic cells within L3T4-Lyt-2-Ia-Mac- cells.

Bone marrow-derived precursors colonize the thymus, where they constitute the minor L3T4-Lyt2- subset which can give rise to all thymocyte subpopulations. We show in the present paper that L3T4-Lyt2- population depleted of Ia+, Mac-1+ cells contain pluripotent hemopoietic stem cells (CFU-S) and granulocyte-macrophage colony-forming cells (GM-CFC). Addition of GM-CSF to the culture medium leads to the production of adherent and nonadherent cells of the macrophage-monocyte lineage. L3T4-Lyt2- cells poorly respond to IL-2 in vitro, but the addition of either rIL-3 or rGM-CSF allows the IL-2 response of L3T4-Lyt2- cells. This response is at least partly mediated by maturation of double-negative cells for L3T4 and Lyt-2 Ag into cells able to produce IL-1.

Animals↗

PubMed1985

Functional analysis of T cell subsets from mice bearing the lpr gene.

The autosomal recessive lpr (lymphoproliferation) gene is responsible for a thymus-dependent massive lymphoproliferation associated with the development of lupus-like autoimmune disease. Phenotypic analysis of adult lpr/lpr lymph nodes has demonstrated accumulation of a dull Lyt-1+, Thy-1+ population that expresses neither Lyt-2 nor L3T4 antigens. With the use of a depletion method based on complement-mediated lysis with an anti-Lyt-2 monoclonal antibody (31 M) and a new anti-L3T4 monoclonal antibody (RL 172.4), we have purified the Lyt-2- L3T4- subset from lymph nodes or spleens of C57BL/6-lpr/lpr mice and determined whether they are immunologically functional in vitro. Production of neither interleukin 2 nor interferon-gamma was detected by the double-negative subset after stimulation with concanavalin A and/or phorbol myristate acetate. The frequencies of allospecific cytotoxic T lymphocyte (CTL) precursors and lectin-induced antigen-nonspecific CTL precursors were diminished to almost undetectable levels, whereas the Lyt-2+ population from lpr/lpr mice had CTL-precursor frequencies comparable with that of +/+ mice. These results show that the major cell subset of adult lpr/lpr lymph nodes or spleens is composed of lymphocytes with markedly limited potential for lymphokine production or antigenic stimulation.

Animals↗

PubMed1995

Differential expression of integrins on human thymocyte subpopulations.

Integrins represent a candidate group of cell surface receptors that may control the homing and population of the thymus by T-cell precursors and the subsequent migration of developing thymocytes through the thymic architecture. We have used multiparameter flow cytometric methods to characterize the expression of several members of the integrin family (alpha 3 beta 1, alpha 4 beta 1, alpha 5 beta 1, alpha 6 beta 1, and alpha L beta 2) on thymocyte subpopulations and have correlated integrin expression with other well-defined thymocyte differentiation markers. alpha 4 beta 1 was expressed by all thymocytes, but expression was highest on CD4-CD8- double-negative (DN) cells, high on CD+CD8+ double-positive (DP) cells, and lowest on mature single-positive (SP) cells, alpha 3 beta 1, alpha 5 beta 1, and alpha 6 beta 1 were present on 13%, 63%, and 26% of thymocytes, respectively, with maximal levels of expression on DN and SP cells, and low levels of expression on DP cells. Simultaneous analysis of alpha 4 beta 1, alpha 5 beta 1, and CD3 expression suggested a pathway of T-cell differentiation in the thymus in which the majority of the DN cells were alpha 4 beta 1hi alpha 5 beta 1hi, the DP cells alpha 4 beta 1hi alpha 5 beta 1lo/-, and the most mature SP cells were alpha 4 beta 1int. The stage-specific expression of integrins strongly implies their functional involvement during T-cell maturation in the thymus.

Cell Differentiation↗

PubMed1994

In vivo CD4+ lymph node T cells from lpr mice generate CD4-CD8-B220+TCR-beta low cells.

Double-negative CD4-CD8-T cells (DNT) have been shown to be the major population of T cells responsible for the massive lymphadenopathy associated with the early onset of the lupus-like syndrome in mice bearing the lpr gene. Previously, we demonstrated that these cells do not proliferate in the peripheral lymphoid organs that they invade; furthermore, we showed that a wide range of CD4 Ag expression was observed on lymph node CD4+ T cells. In this study, we used an in vivo transfer system to analyze the progeny of CD4+ T cells from B6-lpr/lpr mice. Purified CD4+ T cells injected into B6 nude mice are able to generate DNT cells; furthermore, phenotypic and functional characterizations of the DNT cells generated in vivo show that they share the same properties as DNT cells from B6-lpr/lpr mice. We also show that, after in vitro bromodeoxyuridine incorporation, only CD4+ cells cycle. From these studies, we conclude that the lymphoproliferation occurs at the CD4+ stage and that down-regulation of this Ag probably is followed by arrest of the cell cycle.

Animals↗

PubMed1995

Human CD4-CD8- alpha beta + T-cell receptor T cells recognize different mycobacteria strains in the context of CD1b.

Double-negative alpha beta+ T-cell receptor (TCR) human T cells have been reported to recognize antigen in the context of the HLA class I-like (Ib) CD1 complex. In particular, the CD1b molecule has been shown to act as the element of genetic restriction for antigens derived from Mycobacterium tuberculosis. The stenotopic nature of these major histocompatibility complex (MHC) class Ib molecules raised the question of whether the antigenic moiety recognized by CD4-CD8- alpha beta+ TCR T cells was shared by different mycobacteria. We demonstrate here that a CD4-CD8- alpha beta+ TCR T-cell line and three clones raised against M. tuberculosis proliferated following stimulation with soluble extracts from organisms of the M. tuberculosis complex, M. leprae and 10 out of 16 tested isolates of M. avium complex; however, four species of weakly or non-pathogenic mycobacteria were not stimulatory. Furthermore, the M. tuberculosis soluble extract (MTSE)-derived, recognized antigenic moiety proved to be proteinase K resistant and to have a molecular weight greater than 5000 MW, thus it differed from the reported antigenic moiety, recognized by CD4-CD8- gamma delta+ TCR cells. Our results suggest that a common antigenic moiety, presented by CD1b molecules to CD4-CD8- alpha beta+ TCR T cells, is shared by many mycobacterial species. Therefore they raise interest in the question of whether CD4-CD8- alpha beta+ TCR T cells, elicited by M. tuberculosis, may play a role in the natural history of other mycobacterial infections.

Antigens, Bacterial↗

PubMed1995

Comparison of p56lck and p59fyn protein expression in thymocyte subsets, peripheral T cells, NK cells, and lymphoid cell lines.

The expression of the src-family kinases, p56lck and p59fyn, is critical for thymocyte development and TCR-mediated signal transduction, and may be important for signaling through other lymphoid receptors as well. Overexpression studies have demonstrated that the levels of p56lck and p59fyn expression can affect T cell development and signaling through the TCR. Therefore, it is likely that their exact expression levels play an important role in modulating signaling in thymocytes, mature T cells, and other lymphocytes. Here, we used quantitative immunoblotting to measure p56lck and p59fyn protein expression levels in thymocyte subsets, peripheral T cells, NK cells, and lymphoid cell lines. p59fyn expression levels were similar to p56lck in most cells that were examined demonstrating that p59fyn is abundantly expressed in T cells. In addition, we found that p56lck protein expression is equivalent in CD4 and CD8 double-negative, double-positive, and single-positive thymocytes. In contrast, p59fyn expression levels were significantly lower in double-positive thymocytes than in the other thymocyte subpopulations. Finally, we demonstrate that p56lck and p59fyn expression varies greatly in a number of cell lines used to study T cell activation and that IL-2 treatment can dynamically regulate p56lck and p59fyn expression in some cells.

Animals↗

PubMed1995

Relationships between intermediate TCR cells and NK1.1+ T cells in various immune organs. NK1.1+ T cells are present within a population of intermediate TCR cells.

Experiments to date have revealed a population of T cells that carry intermediate (int) levels of TCR (or CD3) and express IL-2R beta-chain (IL-2R beta) in mouse liver. Such int TCR cells also reside in other immune organs, although in low numbers. On the other hand, NK1.1+ T cells with int TCR do reside in the thymus and other peripheral organs. To determine the relationship of two types of cells, we characterized int CD3 cells and NK1.1+ T cells throughout the organs in terms of the phenotype, V beta repertoire, and morphology. Although both IL-2R beta+ T cells and NK1.1+ T cells are classified as int CD3 cells, NK1.1+ T cells are present within int CD3 cells. The majority of int CD3 cells in the liver and thymus were NK1.1+, whereas the minority of such cells in the spleen, lymph nodes, and bone marrow were NK1.1+. Among int CD3 cells, double-negative (DN) CD4-8- cells and/or CD4+ were abundant in NK1.1+ subset, whereas CD8+ cells were generally abundant in NK1.1- subset. Self-reactive V beta+ clones estimated by the M1s system were distributed to both NK1.1+ and NK1.1- subsets. High CD3 cells in the thymus and other organs contained neither DN cells nor forbidden clones. Int CD3 cells had the morphology of granular or agranular lymphocytes carrying perforin. Among int CD3 cells, NK1.1+ subset had a higher level of perforin-positive cells than NK1.1- subset. These results clearly demonstrate the relationship between int TCR cells and NK1.1+ T cells in various organs.

Animals↗

PubMed1993

Sequential analysis of hematopoietic reconstitution achieved by transplantation of hematopoietic stem cells.

We confirmed that murine hematopoietic stem cells express the c-kit molecule but not lymphohematopoietic lineage markers. These lineage marker-negative c-kit-positive (Lin- c-kit+) cells were further divided according to the uptake of rhodamine-123 (Rh-123). Approximately 1,000 Lin- c-kit+ rhodamine-123dull cells, which contained 4.0 +/- 1.3 and 12.5 +/- 1.9 day 8 and day 12 spleen colony-forming units (CFU-S), respectively, rescued the 100% of lethally irradiated mice. One third of these cells formed colonies in the presence of interleukin-3 plus erythropoietin. The time course of the hematopoietic reconstitution of this primitive hematopoietic stem cell fraction was investigated by using Ly-5 congenic mice. Although myeloid cells and B lymphocytes were detected in the peripheral blood 2 to 3 weeks after transplantation, T lymphocytes were not detected until 4 weeks after transplantation. It is generally assumed that myeloid cells and B lymphocytes grow in the bone marrow and that T lymphocytes must pass through the thymus. For the first 2 to 3 weeks after transplantation, donor-type T lymphocytes were not dominant in the thymus, and most donor type cells were CD4/CD8 double-negative or double-positive (including CD4low and CD8low). Four weeks after transplantation, donor-type T lymphocytes were dominant and the ratio of CD4/CD8 cells had recovered to the normal pattern. However, significant numbers of T lymphocytes were detected in the peripheral blood at this stage. Sequential analysis of hematopoietic reconstitution from primitive stem cells demonstrates that myeloid and B-lymphoid lineages occurred earlier than that of the T-lymphoid lineages.

Animals↗

PubMed1995

Characterization of intermediate T-cell receptor cells expanding in the liver, thymus and other organs in autoimmune lpr mice: parallel analysis with their normal counterparts.

Autoimmune MRL-lpr/lpr (lpr) mice were previously demonstrated to have an abnormal proliferation of intermediate T-cell receptor (TCR) cells of extrathymic origin in the liver. Despite this situation, thymectomy in lpr mice resulted in amelioration of autoimmune disease. To understand the underlying mechanism, we investigated associated T-cell differentiation in the thymus and other organs of these mice. When the disease was evoked, T cells with extrathymic properties, i.e. intermediate TCR-alpha beta cells expressing double-negative (DN) CD4-8- phenotype and interleukin-2 (IL-2) receptor beta-chain, became prominent not only in the liver, but also in the thymus. Such thymic T cells mainly resided in the medulla. A small-scale localization of such T cells was seen in the thymic medulla even in normal control mice. There was a heterogeneity among intermediate TCR cells in terms of the composition of DN cells and the expression of CD2 and B220 antigens, depending on the organs and the sites in the same organ. Intermediate TCR cells in the liver, thymus and autoimmune target organs (e.g. kidney) contained a high proportion of the active form (CD2+B220-), while intermediate TCR cells accumulating in peripheral organs, the spleen and lymph nodes, were mainly of the inactive form (CD2-B220+). The active form had an ability to proliferate in response to IL-2 and SEB, whereas the inactive form did not. The present results suggest that the proliferation of intermediate TCR cells occur at multiple sites; this may explain the effect of thymectomy, namely, the retarded onset of disease, in lpr mice.

Animals↗