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A pronounced asymmetry in the recirculation from blood to lymph of resting small recirculating T lymphocytes is described. When 51Cr-labeled small T-recirculating lymphocytes (TRL) from intestinal lymph were infused intravenously their relative recovery in intestinal lymph was about twice that in nodal lymph. In contrast, the relative recovery in nodal lymph of 51Cr-labeled nodal TRL was twice that in intestinal lymph. Intestinal TRL migrated in large numbers through the small intestine. Nodal TRL did not. It is proposed that the pool of recirculating small T lymphocytes consists of two major subdivisions, an intestinal pool and a nodal pool. The nodal circulation comprises small TRL which traverse PCV in all lymph nodes (LN) but not the small intestine. The intestinal circulation comprises small TRL which do not traverse PCV in LN, but which do recirculate through the small intestine from which they pass via afferent lymphatics to the mesenteric LN and subsequently via the thoracic duct into the blood. It is suggested that the intestinal circulation is present in the fetus and that its initial development is independent of extrinsic antigen.

The increased input of RL into LN starts within 3 h after antigenic stimulation and is due to an increase in the number of RL passing through a LN. It is not associated with an altered transit time through a LN of the majority of RL and it cannot occur in the absence of high endothelial PCV. The immediate decrease in the output of RL from an antigen-stimulated LN is due to a delay in the exit from that LN of RL which had entered the LN before antigen was given. The decrease in cell output from a LN after antigen administration affects blast cells produced within the LN as well as small lymphocytes and is not specific for RL. There are at least two distinct mechanisms controlling the migration of RL through an antigen-stimulated LN. The first controls the increased input of RL which occurs only through high endothelial PCV. The second controls the immediate decrease in cell output, which although it does not occur at the level of the high endothelial PCV, can only occur in organized lymphoid tissue. The increased input of RL into an antigen-stimulated LN and the decreased cell output from the LN can occur independently and are possibly controlled by different mechanisms.

Immune responses which give rise to the synthesis of antibodies of restricted heterogeneity can be reproducibly induced in rabbits and mice by streptococcal polysaccharide antigens (1,2). While these reports have demonstrated clonotype restriction in the immune serum of rabbits and mice, they give little information with respect to the clontype restriction in a single reaction site of organized lymphoid tissue, for example a single lymph node. The kinetics of immune responses in lymph nodes in situ have been studied in sheep using a variety of antigens (3-6), and a substantial body of information is available on the changes in cell output, cell type, and the number of antibody-secreting cells which occur within the efferent lymph of antigen-stimulated lymph nodes. However, there is no information with respect to the amount and the heterogeneity of antibody that is secreted by the lymph node or cells within the efferent lymph. In the present report we have examined the temporal sequence of clonal restriction in the efferent lymph of individual sheep popliteal lymph nodes undergoing an immune response to the streptococcal group A-variant polysaccharide (Av-CHO).

Lymphocyte recirculation is critical to maximize the efficiency of immunological surveillance and is an absolute requirement for the development of systemic memory. The consensus view of the lifespan of peripheral T cells holds that naive T cells are long-lived cells and most memory T cells are short-lived cells, although the question of the lifespan of peripheral T cells is not yet fully resolved. We have studied the lifespan of T cells circulating in efferent lymph draining lymph nodes (LN) in the immunologically naive sheep fetus and in postnatal lambs immediately following birth by examining the in vivo incorporation of [3H]thymidine by newly formed T cells during continuous administration of [3H]thymidine. We report that authentically naive fetal T cells are long-lived cells which continue to recirculate between blood and lymph during fetal life. At birth, however, a process is triggered whereby fetal T cells circulating through LN are rapidly lost from the peripheral T cell pool and are replaced by freshly arriving T cells which have been formed since birth. Our results indicate that by the end of the first week of postnatal life, around three-quarters of the T cells circulating through peripheral LN have been formed since birth.

Zusammenfassung Es wird gezeigt, daß es möglich ist, durch ein kreisförmiges Potentiometer, dessen Bürste durch einen Synchronmotor angetrieben wird, die Analyse einer bestimmten Harmonischen hinsichtlich Größe und Phasenlage vorzunehmen. Unter der Voraussetzung, daß die Kopplungsfunktion des Potentiometers eine Sinusfunktion ist, entsteht aus der zugeführten Spannungu=f (x) die Spannung f (x) sinv x, deren arithmethischer, durch ein Drehspulinstrument angezeigter Wert verhältnisgleich dem Koeffizientenav (bv,Av=√ av2+bv2) ist.

THE injection of large doses of antigen into very young animals results in a weakening of the antibody response when a further dose of antigen is administered to the adult animal. This phenomenon has been described as acquired tolerance1, immunological approximation2or immunological unresponsiveness3. It is not yet clear whether the administration of large doses of bacterial antigen during embryogenesis or the first days of postnatal life can also inhibit immunity responses in adult animals. Buxton found a suppression of antibody formation to Salmonella4, and Kerr and Robertson5to Trichomonas foetus. Cohn6and Smith and Bridges7, on the other hand, found no inhibition of antibody production after the injection of bacterial antigens.

IT is generally agreed that the internal environment in new-born animals is not favourable for antibody formation to occur, as has been postulated by Dixon1,2. It has, however, been demonstrated in our laboratory3–5that new-born animals are more suitable recipients for transferred cells producing antibodies—during the period when they are not capable of their own active antibody synthesis6—than X-irradiated adult animals. We suppose that the homotransplantation reaction is the main factor limiting antibody formation by cells transferred to young animals7. Simonsen8has shown that spleen cells of adult hens are tolerated if transferred to chicken embryos three days before hatching. We assumed, therefore, that by using the chicken embryo as recipient it will be possible to obtain fully developed formation of antibodies to bacterial antigens and also a positive primary response to a protein antigen. According to Dixon's assumption, this should, on the other hand, lead to a further decrease in the intensity of antibody formation in embryos.

RECENTLY, Šterzl1used newborn animals as recipients for the transfer of tissues producing antibodies as infant animals cannot produce antibodies after administration of antigens during the early postnatal period2. This experimental model has been used successfully by Mitchison3, who evoked antibody production in chicks after transfer of spleen tissue from strongly immunized hens. Dixon and Weigle4, however, were unable to demonstrate the usefulness of infant animals for the demonstration of antibody formation after transfer of tissues from animals immunized 24 hr. previously. In further work, when cells mixed with antigen in vitro were transferred, results were again negative5. In the work reported here, the possibility of using infant animals soon after birth as recipients was tested.