The primary in vivo immune response to Mls-1 (Mtv-7 sag). Route of injection determines the immune response pattern.
Injection of cells expressing the retroviral superantigen Mls-1 (Mtv-7 sag) into adult Mls-1- mice induces a strong immune response including both T- and B-cell activation. This model was used for studying qualitative aspects of the immune response in normal mice with a defined antigen-presenting cell (the B cell) and without the use of adjuvant. BALB/c mice were injected locally or systemically with Mls-1-expressing spleen cells from Mls-1-congenic BALB.D2 mice. Intravenous injection led to an initially strong expansion of Mls-1-reactive V beta 6+ CD4+ cells mainly in the spleen, to a large degree explained by the trapping of reactive cells, and a rapid down-regulation of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) production, consistent with the proposed tolerogenic property of B cells as antigen-presenting cells. However, these mice developed a slowly appearing but persistent B-cell response dominated by IgG1-producing cells, suggesting a shift in lymphokines produced rather than complete unresponsiveness. Subcutaneous injection into the hind footpad with the same number of cells led to a strong local response in the draining lymph node, characterized by a dramatic increase of V beta 6+ CD4+ T cells, local production of IL-2 and IFN-gamma and a strong but short-lived antibody response dominated by IgG2a-producing cells, characteristic of a T-helper type 1 (Th1) type of response. Both routes of injection led ultimately to deletion of reactive T cells and anergy, as defined by the inability to produce IL-2 upon in vitro stimulation with Mls-1. It is concluded that Mls-1 presented by B cells induces qualitatively different responses in vivo dependent on the route of injection. We propose that the different responses result from the migration of the injected cells to different micro-anatomical sites in the lymphoid tissue. Furthermore, these results suggest that B cells may function as professional antigen-presenting cells in vivo present in an appropriate environment.
Ludwig Institute for Cancer Research, Lausanne Branch, Epalinges, Switzerland.
M
M
Andersson
H
H
Acha-Orbea
D000818:Animals; D000917:Antibody Formation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D017690:Cell Transplantation; D007114:Immunization; D007136:Immunoglobulins / Q000378:metabolism; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D012190:Retroviridae / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018089:Superantigens / Q000008:administration & dosage*
D007136:Immunoglobulins; D007376:Interleukin-2; D018089:Superantigens; D007371:Interferon-gamma