Rac2-deficient mice display perturbed T-cell distribution and chemotaxis, but only minor abnormalities in T(H)1 responses.
The haematopoietic-specific RhoGTPase, Rac2, has been indirectly implicated in T-lymphocyte development and function, and as a pivotal regulator of T Helper 1 (T(H)1) responses. In other haematopoietic cells it regulates cytoskeletal rearrangement downstream of extracellular signals. Here we demonstrate that Rac2 deficiency results in an abnormal distribution of T lymphocytes in vivo and defects in T-lymphocyte migration and filamentous actin generation in response to chemoattractants in vitro. To investigate the requirement for Rac2 in IFN-gamma production and TH1 responses in vivo, Rac2-deficient mice were challenged with Leishmania major and immunized with ovalbumin-expressing cytomegalovirus. Despite a minor skewing towards a T(H)2 phenotype, Rac2-deficient mice displayed no increased susceptibility to L. major infection. Cytotoxic T-lymphocyte responses to cytomegalovirus and ovalbumin were also normal. Although Rac2 is required for normal T-lymphocyte migration, its role in the generation of T(H)1 responses to infection in vivo is largely redundant.
Croker
Ben A
BA
Divisions of Cancer, Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria, South Australia.
Handman
Emanuela
E
Hayball
John D
JD
Baldwin
Tracey M
TM
Voigt
Valentina
V
Cluse
Leonie A
LA
Yang
Feng-Chun
FC
Williams
David A
DA
Roberts
Andrew W
AW
D000199:Actins / Q000378:metabolism; D000818:Animals; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism; D054415:Chemokine CCL19; D019742:Chemokines, CC; D002634:Chemotaxis, Leukocyte; D003587:Cytomegalovirus / Q000276:immunology; D005353:Fibronectins / Q000378:metabolism; D007074:Immunoglobulin G / Q000145:classification / Q000276:immunology; D020104:Immunophilins / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D018320:Leishmania major / Q000166:cytology / Q000276:immunology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019696:Peptidylprolyl Isomerase; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000737:chemistry / Q000276:immunology*; D020744:rac GTP-Binding Proteins / Q000172:deficiency / Q000502:physiology*; D000097766:RAC2 GTP-Binding Protein
D000199:Actins; D015815:Cell Adhesion Molecules; D054415:Chemokine CCL19; D019742:Chemokines, CC; D005353:Fibronectins; D007074:Immunoglobulin G; D020104:Immunophilins; D019012:Integrin beta1; D008565:Membrane Proteins; D019696:Peptidylprolyl Isomerase; D020744:rac GTP-Binding Proteins; D000097766:RAC2 GTP-Binding Protein; C515461:Ccl19 protein, mouse