Expression of MEL-14 antigen is not an absolute requirement for dissemination to lymph nodes after adoptive transfer of murine T lymphocyte clones.
The inability of established antigen-specific murine T lymphocyte clones to recirculate well in vivo has been attributed to loss of the surface glycoprotein gp90MEL-14, which is important for specific adherence to post-capillary high endothelial venules in peripheral lymph nodes (LN). Defective recirculation of clones may contribute to inefficient adoptive immunotherapy when compared with fresh immune spleen or LN populations. To optimize models of adoptive immunotherapy, we sought to improve recirculation of Thy-1.2+, L3T4+ clones by inducing reexpression of MEL-14 antigen (gp90MEL-14). Clones were analyzed after treatment with differentiating agents, incubation in the presence or absence of recombinant interleukin 2 (rIL 2), coincubation in vitro with nonirradiated Thy-1.1 LN or thymus cells, or adoptive transfer into Thy-1.1 hosts. We were unable to demonstrate induction of gp90MEL-14 in any case. However, although clones remained MEL-14 negative, they were able to disseminate widely after subcutaneous adoptive transfer in the presence of clone-specific antigen and rIL 2 into Thy-1.1 mice pretreated with cyclophosphamide. Withdrawal of exogenous rIL 2 was associated with rapid disappearance of clones from all sites. We conclude that murine T cell clones undergo a step in terminal differentiation that precludes surface expression of gp90MEL-14 and that these clones would be unlikely to provide a source of long-lived recirculating memory T lymphocytes. However, under appropriate circumstances it is possible for antigen-specific clones to disseminate widely among host LN and mediate short-term immune responses.
D000818:Animals; D000954:Antigens, Surface / Q000502:physiology*; D002465:Cell Movement; D006023:Glycoproteins / Q000502:physiology; D007116:Immunization, Passive; D008198:Lymph Nodes / Q000166:cytology*; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D013601:T-Lymphocytes / Q000502:physiology*; D013950:Thymus Gland / Q000502:physiology
D000954:Antigens, Surface; D006023:Glycoproteins; D008565:Membrane Proteins