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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]

Human peripheral lymphocyte preparations were tested with a mixed rosette method for the presence of lymphocytes bearing both the complement receptors characteristic of B lymphocytes, anti the capacity of T lymphocytes to spontaneously bind with sheep red blood cells (SR BC). The large and oval shaped pigeon red blood cells (PRBC) which do not form T-cell rosettes were utilized as indicators for rosette formation with the complement receptor-bearing B cell. In every individual (an average of 2.06%) lymphocytes were observed which formed rosettes with both SRBC' and PRBC indicators. These findings show that independent markers for both T and B cells may be present on the surface of the same lymphocytes. [ABSTRACT FROM AUTHOR]

By the use of an indirect immunofluorescent method for the identification of mouse T lymphocytes forming rosettes with antibody-coated erythrocytes, it was found that about 10% of the T cells in normal mouse spleen have receptors for antibody. Inhibition experiments with purified aggregated immunoglobulins showed that IgG2 is the major class involved. The same receptor was found on T cells activated against H-2 isoantigens. The importance of using the appropriate red cells and antiserum for demonstrating receptors of T cells is stressed. [ABSTRACT FROM AUTHOR]

A method is described for indirect immunofluorescent staining of mouse T cells forming rosettes, involving fixation of rosettes by gluturaldehyde and staining with a rabbit anti-mouse brain serum absorbed so as to be specific for T cells. Using this technique, it was shown that about 44%, of spleen cells forming rosettes with sheep erythrocytes both in non-immunized and immunized mice, are T cells. The number of T rosette-forming cells increased about ten-fold after immunization with sheep erythrocytes. but only when serum antibody was detectable. [ABSTRACT FROM AUTHOR]

Mononuclear cell separated from the blood in fourteen cases of infectious mononucleosis at various intervals from the onset were tested for the presence of surface immunoglobulin and for ability to form spontaneous rosettes with washed sheep red blood cells. The mononucleosis during the acute phase of the illness consisted largely of T lymphocytosis. The absolute count of T lymphocytes returned to the normal range approximately 2 months after the onset of the illness. B cells (bearing surface immunoglobulin) were only slightly increased in the acute phase. In four cases appreciable numbers of fluorescent resetting cells were also present, and investigation suggested that these were T cells coated with anti-T-cell autoantibody. During the first 2 weeks of the illness responsiveness to phytohaemagglutinin was severely depressed, but thereafter returned towards normal. It is thought likely that in infectious mononucleosis the vast majority of atypical mononuclear cells are T cells proliferating in response to E-B virus-infected B cells, and cytotoxic towards them. [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]

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]