Attrition of bystander CD8 T cells during virus-induced T-cell and interferon responses.
Experiments designed to distinguish virus-specific from non-virus-specific T cells showed that bystander T cells underwent apoptosis and substantial attrition in the wake of a strong T-cell response. Memory CD8 T cells (CD8(+) CD44(hi)) were most affected. During acute viral infection, transgenic T cells that were clearly defined as non-virus specific decreased in number and showed an increase in apoptosis. Also, use of lymphocytic choriomeningitis virus (LCMV) carrier mice, which lack LCMV-specific T cells, showed a significant decline in non-virus-specific memory CD8 T cells that correlated to an increase in apoptosis in response to the proliferation of adoptively transferred virus-specific T cells. Attrition of T cells early during infection correlated with the alpha/beta interferon (IFN-alpha/beta) peak, and the IFN inducer poly(I:C) caused apoptosis and attrition of CD8(+) CD44(hi) T cells in normal mice but not in IFN-alpha/beta receptor-deficient mice. Apoptotic attrition of bystander T cells may make room for the antigen-specific expansion of T cells during infection and may, in part, account for the loss of T-cell memory that occurs when the host undergoes subsequent infections.
McNally
J M
JM
Department of Pathology, Program in Immunology and Virology, University of Massachusetts Medical School, 55 Lake Ave. N., Worcester, MA 01655, USA.
Zarozinski
C C
CC
Lin
M Y
MY
Brehm
M A
MA
Chen
H D
HD
Welsh
R M
RM
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D018960:Hyaluronan Receptors / Q000032:analysis; D007156:Immunologic Memory; D016898:Interferon-alpha / Q000502:physiology*; D016899:Interferon-beta / Q000502:physiology*; D007371:Interferon-gamma / Q000502:physiology; D007694:Killer Cells, Natural / Q000502:physiology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054353:Perforin; D011070:Poly I-C / Q000494:pharmacology; D052899:Pore Forming Cytotoxic Proteins; D013601:T-Lymphocytes / Q000502:physiology
D018960:Hyaluronan Receptors; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D016899:Interferon-beta; D007371:Interferon-gamma; D011070:Poly I-C