Binding of autologous erythrocytes to immature T-cells.

Abstract

A small percentage of normal mouse thymus and spleen lymphocytes form rosettes with autologous erythrocytes. The number of these autologous rosettes increases 15-to 20-fold after adult thymectomy and to a lesser degee with aging. Autologous rosette level is also abnormally high in nude (congenitally athymic) mice. The high level of autolo gous rosette-forming celmsfound after adult thymectomy is normalized by injecting ng amounts of purified circulating thymic factor. Autologous rosette-forming cells adhere to nylon, belong to the less dense spleen cells, are in majority steroid-resistant in the thymus. All these properties suggest that autologous rosette-forming cells might belong to immature T-cell (thymic-dependent cell) precursors. Thymic-dependent cell (T-cell) maturation involves several steps from the primitive stem cell to the fully competent peripheral T-cell (1-5). The difficulties in visualizing these different steps come from the absence of morphological criteria available for other blood cell lineages or of markers used to distinguish B-and T-cells.A small percentage of normal mouse lymphoid cells bind autologous erythrocytes, forming rosettes. These autologous rosette-forming cells (A-RFC) are found predominantly in the thymus and at lower percentages in the spleen (6, 7). A-RFC have elicited a great interest because of their potential use as a model of self-recognition (6, 7). We report here that A-RFC level in the spleen is dramatically increased after adult thymectomy and that purified thymic hormone corrects such increase.These data and others, also presented here, suggest that autologous rosette formation may be a selective property of immature T-cells which could eventually be used as a marker of this cell population.MATERIAL AND METHODS Mice. Male and female mice of the CBA-H (histocompatibility type H-2k) or C57BI/6 (H-2b) strains were used in most experiments. In some cases, nude (congenitally athymic) mice were also utilized. When not specified, the mice were 6-8 weeks old. Thymectomies were performed by suction; "thymus-deprived" mice were prepared by thymectomy followed by irradiation (850 rads) and reconstitution by intravenous (i.v.) injection of 15 X 106 syngeneic bone marrow cells.Antitheta Serum (AOS). This was prepared by injecting 107 CBA thymocytes intraperitoneally (i.p.) into AKR mice once weekly for 8 weeks (5).

Rosette formation between murine lymphocytes and erythrocytes. A new locus in the H-2 region.

“…Koskimies and M~ikel~i (18) reported that T-cell-deficient mice made stronger anti-hapten responses to conjugates of syngeneic erythrocytes than to conjugates of allogeneic or xenogeneic erythrocytes. These findings, together with others demonstrating that an appreciable fraction of murine lymphocytes form rosettes with autologous, but not with isologous, erythrocytes (19)(20), support the existence on at least some immunocytes of a receptor for a self-marker which is expressed on erythrocytes.Because this form of self-recognition is likely to be of significance for a complete understanding of the mechanisms of lymphocyte activation, it was of interest to further investigate the phenomenon of autologous rosette formation. The present study confirms the phenomenon, establishes that the receptor in question is expressed on both T and B lymphocytes, and that it is not immunoglobulin in nature.…”

Autologous rosette-forming T cells regulate responses of T cells. Phenotypic and functional analysis of suppressor cells generated from autologous rosette-forming T cells after autologous mixed lymphocyte reactions.

“…It is also of considerable interest that the phenomenon of autorosette-forming thymocytes can also be observed in the mouse (26,27). In this species, however, the ability to form rosettes requires histocompatibility in the L region between the T lymphocyte and the mouse erythrocytes (28)(29)(30).…”

Establishment of the specific radioimmunoassay for serum thymic factor(STF).

“…For this reason, the , specificity of R 0116-5 for STF was tested. Binding ratio of R 0116-5 to STF (4-9) was the same as that to STF, while binding to STF (6-9) and STF (8)(9) were not observed at all. Furthermore, R 0116-5 was unable to bind to 125I-[Tyr10]-STF.…”

“…To characterize the specificity of the anti-STF anti-serum, the capacities of its binding to STF fragments, STF (4-9), STF (6-9), and STF (8)(9) which are composed of C-terminal 6, 4, or 2 amino acids, were measured. Also, the c:rossreactivities of the antiserum with various gastrointestinal peptides, gastrin 17, gastrin 34 (1-15), cholecystokinin (non-sulfate), porcine gastrin releasing peptide, substance P, glucagon, neurotensin or vasoactive intestinal polypeptide, were examined.…”

“…STF is a peptide composed of nine amino acids and its molecular weight is 857 ; Pleau et al 1977). The biological activities of STF have been reported as follows ; 1) conversion of 8 antigen on T cells in vivo (Bach et al 1975a) and in vitro (Fournier and Bach 1975), 2) enhancement of the generation of alloantigen reactive cytotoxic T cells in thymectomized mice (Bach and Beaurain 1976), 3) induction of suppressor T cells in New Zealand Black mice (Bach and Niandet 1976), 4) enhancement of mitogen response of lymphocyte in nude mice in vitro (Bach et al 1975b ), and 5) normalization of the abnormally high level of autologous erythrocyte-binding cells in adult thymectomized mice (Charreire and Bach 1975). Clinically, the relationship between STF and zinc deficiency in human has been reported (Prasad et al 1988).…”