The Immunologically Specific Retention of Recirculating Long-Lived Lymphocytes in Lymph Nodes Stimulated by Xenogeneic Erythrocytes

Abstract

We have previously demonstrated that lymph nodes draining the site of an allograft reaction selectively retain long-lived lymphoid cells, in part on the basis of the immunological specificity of the cells involved (1). The relatively small immunologically specific component in this accumulation was demonstrated by a double isotope dilution method, in which cells sensitized to one set of histocompatibility antigens were labeled in vivo with thymidine-3H and cells sensitized to a different set of histocompatibility antigens were labeled with thymidine-~4C, under conditions where most of the label was confined to the long-lived cells (1-3). The ceils were then pooled and adoptively transferred to syngeneic hosts who were then challenged with both sets of antigens. Immunological specificity was inferred from the small but consistent excess of cells from the donors immunized to each set of antigens in the lymph nodes stimulated by that same antigen 6-8 days after challenge grafting. In these initial studies (1) we deliberately selected an immunological reaction that was principally dependent on cell-mediated immunity (an allograft reaction in H-2-compatible strains). The present studies were designed to ascertain whether a similar selective accumulation of long-lived lymphocytes occurs in lymph nodes stimulated by antigens evoking principally an immunoglobulin-mediated response, and to demonstrate a similar immunologically specific component in this accumulation.

On T Cell Memory: Arguments for Antigen Dependence

“…Taken together, specific CD8+ T cells accumulated in lymph nodes draining the site of primary infection for approximately one month, suggesting that antigen persisted at least for this duration. The duration of specific T cell accumulation found here is comparable to the duration of T cell accumulation found after injection of several other protein antigens (Thursh & Emeson 1972, Jacobsen & Thorbecke 1969, Smith et al 1970, Stavitsky & Folds 1972. Durkin & Thorbecke 1972.…”

“…Although never discussed in this context, accumulation of CD4+ T cells in lymph nodes where antigen persists, is frequently exploited: in order to obtain optimal antigen-specific proliferation, T cells have to be isolated from lymph nodes draining the site of immunization {Corradin et al 1977, Alkan 1979; secondary CD4+ T cell responses cannot be obtained from distant lymph nodes (Corradin et al 1977). Several other earher studies have found preferential accumulation of memory T and B cells in lymph nodes draining the site of primary immunization for months (Thursh & Emeson 1972, Jacobsen & Thorbecke 1969, Smith et al 1970, Stavitsky & Folds 1972, Durkin & Thorbecke 1972.…”

“…Such exogenous protein antigens enter the class I pathway only inefficiently (Germain 1986, Yewdell & Bennink 1990, but in this case, this fact may even be beneficial in that antigen depots are not emptied too fast. Interestingly, earlier studies using various non-replicating antigens found preferential accumulation of memory lymphocytes in lymph nodes draining the site of injection that lasted for weeks up to a few months (Thursh & Emeson 1972, Jacobsen & Thorbecke 1969, Smith et al 1970. Stavitsky & Foid.s 1972.…”

Architectural alteration of lymphatic tissue produced by extracorporeal thoracic duct filtration

“…Additional supporting studies (Emeson and Thursh,197 1) initially demonstrated by double isotope dilution that lymph nodes draining the site of an allograft reaction selectively retained long-lived lymphoid cells that were of the cell-mediated immune system. A subsequent investigation by these same authors (Thursh and Emeson, 1972) presented evidence that there was also accumulation of long-lived lymphocytes in lymph nodes stimulated by antigens evoking principally an immunoglobulin-mediated response.…”

Competition for cytotoxic immune capacity against A ‘syngeneic’ mouse tumour distributed at two sites

“…Among the most carefully controlled experiments are those of Thursh and Emeson (1972;. These authors immunized groups of mice with either sheep or chicken red blood cells.…”