CD8(+) T cells secreting type 2 lymphokines are defective in protection against viral infection.
Effector T cells secreting type 1 and/or type 2 lymphokines (Tc1, Tc0, Tc2) were generated in vitro from CD8(+) T cells of mice with a transgenic TCR recognizing lymphocytic choriomeningitis virus (LCMV) glycoprotein to compare their effector function in vitro and in vivo. Tc1, Tc2, and Tc0 showed similar Fas- and perforin-mediated cytotoxicity in vitro. Upon adoptive transfer, Tc2 and Tc0 effectors were less efficient than Tc1 at controlling LCMV or recombinant vaccinia virus expressing the LCMV glycoprotein in vivo. Tc2 and Tc0 had decreased surface VLA-4 density and deficient activation-induced LFA-1/ICAM-1-dependent homotypic adhesion in vitro. Therefore, the reduced antiviral activity in vivo of Tc2 and Tc0 compared with Tc1 is not due to reduced cytotoxic activity or IFN-gamma secretion but may be explained by defective homing to the target organ due to decreased expression and/or lower activity of adhesion molecules.
Wirth
S
S
Allergy Unit, Division of Immunology and Allergy, Hôpital Cantonal Universitaire, Geneva, Switzerland.
van den Broek
M
M
Frossard
C P
CP
Hügin
A W
AW
Leblond
I
I
Pircher
H
H
Hauser
C
C
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000821:virology*; D002634:Chemotaxis, Leukocyte; D003601:Cytotoxicity Tests, Immunologic; D039041:Integrin alpha4beta1; D016023:Integrins; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008222:Lymphokines / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D016201:Receptors, Lymphocyte Homing
D039041:Integrin alpha4beta1; D016023:Integrins; D015848:Interleukin-5; D016169:Lymphocyte Function-Associated Antigen-1; D008222:Lymphokines; D011948:Receptors, Antigen, T-Cell; D016201:Receptors, Lymphocyte Homing; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4