CD40 ligand-mediated interactions are involved in the generation of memory CD8(+) cytotoxic T lymphocytes (CTL) but are not required for the maintenance of CTL memory following virus infection.
CD8(+) cytotoxic T lymphocytes (CTL) play a key role in the control of many virus infections, and the need for vaccines to elicit strong CD8(+) T-cell responses in order to provide optimal protection in such infections is increasingly apparent. However, the mechanisms involved in the induction and maintenance of CD8(+) CTL memory are currently poorly understood. In this study, we investigated the involvement of CD40 ligand (CD40L)-mediated interactions in these processes by analyzing the memory CTL response of CD40L-deficient mice following infection with lymphocytic choriomeningitis virus (LCMV). The maintenance of memory CD8(+) CTL precursors (CTLp) at stable frequencies over time was not impaired in CD40L-deficient mice. By contrast, the initial generation of memory CTLp was affected. CD40L-deficient mice produced lower levels of CD8(+) CTLp during the primary immune response to LCMV than did wild-type controls, despite the fact that the LCMV-specific effector CTL response of CD40L-deficient mice was indistinguishable from that of control animals. The differentiation of naïve CD8(+) T cells into effector and memory CTL thus involves pathways that can be discriminated from each other by their requirement for CD40L-mediated interactions. Expression of CD40L by CTLp themselves was not an essential step during their expansion and differentiation from naïve CD8(+) cells into memory CTLp; instead, the reduction in memory CTLp generation in CD40L-deficient mice was likely a consequence of defects in the CD4(+) T-cell response mounted by these animals. These results thus suggest a previously unappreciated role for CD40L in the generation of CD8(+) memory CTLp, the probable nature of which is discussed.
Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA.
P
P
Borrow
D F
DF
Tough
D
D
Eto
A
A
Tishon
I S
IS
Grewal
J
J
Sprent
R A
RA
Flavell
M B
MB
Oldstone
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D023201:CD40 Ligand; D006182:H-Y Antigen / Q000276:immunology; D006412:Hematopoietic Stem Cells; D007156:Immunologic Memory / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D006182:H-Y Antigen; D008562:Membrane Glycoproteins; D023201:CD40 Ligand