The Effect of Antigen Stimulation on the Migration of Mature T Cells from the Peripheral Lymphoid Tissues to the Thymus

Journal of Immunology Research, Aug 2018

Although the maturation and export of T cells from the thymus has been extensively studied, the movement of cells in the opposite direction has been less well documented. In particular, the question of whether T cells which have been activated by antigen in the periphery are more likely to return to the thymus had been raised but not clearly answered. We examined this issue by activating T cells present in the periphery with their cognate antigen, and assessing migration to the thymus. TCR-transgenic cells from OT-I mice (Thy1.2

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The Effect of Antigen Stimulation on the Migration of Mature T Cells from the Peripheral Lymphoid Tissues to the Thymus

Developmental Immunology The Effect of Antigen Stimulation on the Migration of Mature T Cells from the Peripheral Lymphoid Tissues to the Thymus , CHARLES L. HARDY DALE I. GODFREY and ROLAND SCOLLAY Medical Research Council of Australia. Rd." 0 Prahran 0 Australia 0 . Tel: 0 . Fax: 0 . Email: 0 0 From the Centenary Institute of Cancer Medicine and Cell Biology , Locked Bag no 6, Newtown, NSW , Australia , 2042 Although the maturation and export of T cells from the thymus has been extensively studied, the movement of cells in the opposite direction has been less well documented. In particular, the question of whether T cells which have been activated by antigen in the periphery are more likely to return to the thymus had been raised but not clearly answered. We examined this issue by activating T cells present in the periphery with their cognate antigen, and assessing migration to the thymus. TCR-transgenic cells from OT-I mice(Thyl.2/), which recognlse the ovalbumin peptide OVA257_264 in the context of H-2Kb, were transferred into otherwise unmanipulated Thyl.1 / C57BL/6 mice. Recipient mice were injected i.v. with 5 ktg peptide (SIINFEKL) approximately 24 hours later. The numbers of donor-derived (Thyl.2+) cells in the thymus and peripheral lymphoid tissue were determined. The results clearly show increased numbers of transgenic cells in the thymus 3 days after antigenic stimulation. However, since numbers of transgenic cells increased in the spleen and LN in about the same proportion, the data do not support the notion that there is highly increased selective migration of activated T cells to the thymus. Rather, they suggest that a sample of peripheral cells enters the thymus each day, and that the mature immigrants detected in the thymus merely reflect the contents of the peripheral T cell pool. Abbreviations: CFSE, carboxy fluorescein (diacetate) succinimidyl ester; LN, lymph node; MLN, mesenteric lymph node; OT-I mice, OVA257_264-specific TCR-transgenic mice; OVA257_264, ovalbumin peptide Thymus; T lymphocytes; Homing; Recirculation; Transgenic INTRODUCTION The thymus is the primary source of T cells for the peripheral lymphoid organs. T cells produced in the thymus migrate to the spleen and lymph nodes (LN), especially early in life, and in the absence of a thymus these organs remain essentially devoid ofT cells. This pathway has been extensively quantitated in a number of species, and in young adult animals represents an export rate of about 1% of thymocytes per day (Scollay et al., 1980; Scollay and Shortman, 1985) . The reverse pathway, of mature T cells migrating from the periphery back into the thymus is less often considered, although several studies have shown that this is not a major pathway in normal animals (Dumont et al., 1984; Michie et al., 1988; Hirokawa et al., 1989; Agus et al., 1991) . Our own unpublished data suggest that about 1% of the mature phenotype cells in the thymus may be mature T cell immigrants (Coward and Scollay, in preparation). Some studies have suggested that this pathway might preferentially be used by activated T cells. An early report indicated that activated antigen-specific T cells migrated to the thymus, and persisted there, whereas migration of non-activated cells to the thymus was not detected (Naparstek et al., 1982). Similarly, Fink et al. (1984) demonstrated that peripheral T cells activated in vivo provide a greater contribution to the thymic memory CTL response than non-activated cells. In that study, it was not possible to determine the proportion of thymocytes which were donor derived. More recently, it was shown that blasts (generated in parent F combinations) homed to the thymus, and represented approximately 0.4% of mature T thymocytes, although the rate of homing was greatly increased by irradiation of hosts (Agus et al., 1991) . Others have shown that, compared to ?naive? CD4+ T cells, there is a preferential accumulation of antigen-experienced T cells in the rat thymus (Bell et al., 1995; Westerman et al., 1996) . As is the case for ?normal? peripheral T cells (Hirokawa et al., 1989) , accumulation of activated cells within the thymus is largely restricted to the medulla (Pabst and Binns, 1989; Agus et al., 1991; Westermann et al., 1996) . One shortcoming of the above studies is that thymic immigration of in vivo-activated clonal T cell populations has not been analysed. As part of a longer study on migration of mature cells into the thymus, we have addressed this question in a model where TCR transgenic T cells present only in the periphery could be stimulated with their cognate peptide, and their migration to the thymus assessed. OT-I mice (Hogquist et al., 1994) carry a transgene for a MHC class I-restricted TCR with Vc2 and V135 variable regions. The TCR recognises the ovalbumin peptide OVA257_264 presented by H-2Kb, the MHC haplotype of C57BL/6 mice. In these mice, the great majority of peripheral T cells are CD8/CD4-, (...truncated)


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Charles L. Hardy, Dale I. Godfrey, Roland Scollay. The Effect of Antigen Stimulation on the Migration of Mature T Cells from the Peripheral Lymphoid Tissues to the Thymus, Journal of Immunology Research, 8, DOI: 10.1155/2001/20728