In vivo function of homing receptors participating in lymphocyte recirculation: transfer analysis in SCID mice.
In order to examine the in vivo function of the adhesion molecules implicated in lymphocyte homing, blocking effects of antibodies against various adhesion molecules on lymphocyte migration were tested in SCID mice into which BALB/c donor splenocytes had been transferred. It was proved that the transferred donor splenocytes migrated to peripheral lymph nodes (LNs) of SCID mice. T and B lymphocytes were distributed in the specialized compartments as seen in the LNs of normal mice. Migration of lymphocytes to the local LNs was accelerated by stimulation with ovalbumin and complete Freund's adjuvant. This experimental system with accelerated migration was applied to analyze the in vivo function of adhesion molecules, and the following findings were obtained. Combined use of antibodies against lymphocyte-function-associated antigen 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1) strongly inhibited the migration of T lymphocytes to the peripheral LNs. Antibodies against very late antigen 4 (VLA-4) and vascular cell adhesion molecule 1 (VCAM-1) led to diminished B lymphocyte migration and disturbed compartmentalization of T lymphocytes in the paracortex. Migration of both T and B lymphocytes to the LNs was completely inhibited by the antibody against L-selectin. These results indicate that L-selectin plays an essential role in migration of both T and B lymphocytes into peripheral LNs but LFA-1/ ICAM-1 and VLA-4/VCAM-1 play different roles in compartmentalization of T and B lymphocytes in the peripheral LNs. In contrast, these adhesion molecules were not involved in lymphocyte migration to the splenic white pulp, indicating that the mechanisms for lymphocyte homing to the white pulp are quite different from those to the peripheral LNs.
Saito
S
S
Institute of DNA Medicine, Jikei University School of Medicine, Tokyo, Japan.
Kuwashima
N
N
Koizumi
H
H
Nomura
T
T
Yagita
H
H
Okumura
K
K
Sonoda
A
A
Tadakuma
T
T
Tanaka
H
H
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D001402:B-Lymphocytes / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects; D005620:Freund's Adjuvant / Q000494:pharmacology; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D019041:L-Selectin / Q000502:physiology; D008198:Lymph Nodes / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D017710:Lymphocyte Transfusion; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D010047:Ovalbumin / Q000494:pharmacology; D016201:Receptors, Lymphocyte Homing / Q000502:physiology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology
D019138:Antibodies, Blocking; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin; D010047:Ovalbumin; D005620:Freund's Adjuvant