The Specific Selection of Recirculating Lymphocytes by Antigen in Normal and Preimmunized Rats

Abstract

Thoracic duct lymphocytes (TDL) from normal rats will restore a primary antibody response to sheep erythrocytes (SRBC) in irradiated recipients and cause a graft-versus-host reaction in F1 hybrid rats; lymphocytes from rats immunized with either tetanus toxoid or dinitrophenylated bovine gamma globulin (DNP BGG) will generate specific antibody after cell transfer and challenge. The ability of TDL to mediate each of these responses is severely depressed by giving a single intravenous dose of the specific antigen shortly before cannulation of the thoracic duct, although the lymphocyte donors themselves respond normally. The injection of antigen does not decrease the output of lymphocytes in the thoracic duct and the effect is specific for the antigen injected. The findings are most readily accounted for by assuming that small subpopulations of specific lymphocytes are selected from the recirculating pool by antigen which has localized in lymphoid tissue. The observation that passive antibody abolishes selection by SRBC supports this interpretation. The strong selection exerted by a subcutaneous injection of SRBC in Freund's complete adjuvant, which induces delayed hypersensitivity but little early antibody, suggests that a common cell type may be involved in the induction of both delayed hypersensitivity and antibody formation. The anti-DNP antibody response generated by TDL from rats immunized with DNP BGG was abolished by a selecting injection of the homologous conjugate. The response was depressed to a smaller degree by injections of either BGG or dinitrophenylated human serum albumin, suggesting that carrier-specific (T) and hapten-specific (B) lymphocytes could be separately selected from the recirculating pool. The regional selection of recirculating lymphocytes by antigen may explain a number of phenomena in which the prior injection of antigen has been found to inhibit a subsequent immune response.

Influence of Dose and Route of Antigen Injection on the Immunological Induction of T Cells

“…It can be concluded, therefore, that specifically sensitized lymphocytes, once formed, are not subject to specific trapping by antigen alone. This conclusion is supported by the fact that cells which can support an immune response to SRBC have been shown to reappear and be fully represented in central lymph 4 days after an intravenous injection of SRBC (25). At this time, DTH remains fully suppressed in mice immunized intravenously with a comparable dose of SRBC (Figs.…”

“…The present studies show that animals previously sensitized by a footpad injection of SRBC remained fully sensitive for at least 24 h after a massive intravenous injection of SRBC (Fig. 2), yet the phenomenon of selective trapping occurs within 24 h of injecting antigen (25). It can be concluded, therefore, that specifically sensitized lymphocytes, once formed, are not subject to specific trapping by antigen alone.…”

“…No doubt this efltux of cells includes the specific mediators of DTH which are known to b e represented in central lymph (29). It is pertinent, too, that a subcutaneous injection of SRBC in Freund's complete adjuvant caused the same selective removal of reactive cells from central lymph (25), yet DTH appeared in due course. Obviously, the cells that mediate DTH reactions are not retained for long at the site of the primary immune response whether this occurs centrally or in peripheral lymphoid tissues.…”

“…An intravenous injection of SRBC causes prompt withdrawal of specifically responsive lymphocytes from the recirculating lymphocyte pool (25). As a result, thoracic duct lymph becomes depleted of cells which can render irradiated recipients responsive to SRBC.…”

“…As a result, thoracic duct lymph becomes depleted of cells which can render irradiated recipients responsive to SRBC. Though it is not yet certain which cell type is most affected by this process of selective trapping, Rowley et al (25) give reasons for believing that both T cells and B cells are involved. It may be asked, therefore, whether animals fail to display DTH after an excessive dose of SRBC merely because reactive cells are trapped in a central organ such as the spleen.…”