TY - JOUR
T1 - Virus-induced non-specific signals cause cell cycle progression of primed CD8(+) T cells but do not induce cell differentiation
AU - Ørding Andreasen, Susanne
AU - Christensen, Jan Pravsgaard
AU - Marker, O
AU - Thomsen, Allan Randrup
N1 - Keywords: Animals; Antigens, CD44; Antigens, Viral; CD8-Positive T-Lymphocytes; Cell Cycle; Cell Line; Cytotoxicity Tests, Immunologic; Female; Flow Cytometry; Glycoproteins; Lymphocyte Activation; Lymphocytic choriomeningitis virus; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Peptide Fragments; Poly I-C; Receptor-CD3 Complex, Antigen, T-Cell; Receptors, Interferon; T-Lymphocyte Subsets; Time Factors; Vesicular stomatitis Indiana virus; Viral Proteins; Virus Diseases
PY - 1999
Y1 - 1999
N2 - In this report the significance of virus-induced non-specific T cell activation was re-evaluated using transgenic mice in which about half of the CD8(+) T cells expressed a TCR specific for amino acids 33-41 of lymphocytic choriomeningitis virus glycoprotein I. This allowed tracing of cells with known specificity and priming history in an environment also containing a normal heterogeneous CD8(+) population which served as an intrinsic control. Three parameters of T cell activation were analyzed: cell cycle progression, phenotypic conversion and cytolytic activity. Following injection of the IFN inducer poly(I:C), proliferation of memory (CD44(hi)) CD8(+) T cells but no phenotypic or functional activation was observed. Following injection of an unrelated virus [vesicular stomatitis virus (VSV)], naive TCR transgenic cells did not become significantly activated with respect to any of the parameters investigated. In contrast, memory TCR transgenic cells were found to proliferate extensively early after VSV infection (day 0-3), whereas limited proliferation was observed later (day 3-6) when proliferation of non-transgenic CD8(+) T cells is maximal. This aborted response did not result from anergy to TCR stimulation, as memory TCR transgenic cells proliferated vigorously upon stimulation with their nominal peptide. Despite the massive proliferation of memory cells observed early after VSV infection, no phenotypic or functional activation was observed. Together these findings indicate that both non-specific and antigen-specific signals contribute to the initial virus-induced proliferation of CD8(+) T cells, but for further proliferation and differentiation to take place, TCR-ligand interaction is required. The implications for maintenance of T cell memory is discussed.
AB - In this report the significance of virus-induced non-specific T cell activation was re-evaluated using transgenic mice in which about half of the CD8(+) T cells expressed a TCR specific for amino acids 33-41 of lymphocytic choriomeningitis virus glycoprotein I. This allowed tracing of cells with known specificity and priming history in an environment also containing a normal heterogeneous CD8(+) population which served as an intrinsic control. Three parameters of T cell activation were analyzed: cell cycle progression, phenotypic conversion and cytolytic activity. Following injection of the IFN inducer poly(I:C), proliferation of memory (CD44(hi)) CD8(+) T cells but no phenotypic or functional activation was observed. Following injection of an unrelated virus [vesicular stomatitis virus (VSV)], naive TCR transgenic cells did not become significantly activated with respect to any of the parameters investigated. In contrast, memory TCR transgenic cells were found to proliferate extensively early after VSV infection (day 0-3), whereas limited proliferation was observed later (day 3-6) when proliferation of non-transgenic CD8(+) T cells is maximal. This aborted response did not result from anergy to TCR stimulation, as memory TCR transgenic cells proliferated vigorously upon stimulation with their nominal peptide. Despite the massive proliferation of memory cells observed early after VSV infection, no phenotypic or functional activation was observed. Together these findings indicate that both non-specific and antigen-specific signals contribute to the initial virus-induced proliferation of CD8(+) T cells, but for further proliferation and differentiation to take place, TCR-ligand interaction is required. The implications for maintenance of T cell memory is discussed.
M3 - Journal article
C2 - 10464167
SN - 0953-8178
VL - 11
SP - 1463
EP - 1473
JO - International Immunology
JF - International Immunology
IS - 9
ER -