title: Human CD8⁺ and CD4⁺ T cell memory to lymphocytic choriomeningitis virus infection.
abstract: Although cellular immunity to acute lymphocytic choriomeningitis virus (LCMV) infection has been well characterized in experimental studies in mice, the T cell response to this virus in humans is incompletely understood. Thus, we analyzed the breadths, magnitudes, and differentiation phenotypes of memory LCMV-specific CD8(+) and CD4(+) T cells in three human donors displaying a variety of disease outcomes after accidental needle stick injury or exposure to LCMV. Although only a small cohort of donors was analyzed at a single time point postinfection, several interesting observations were made. First, we were able to detect LCMV-specific CD8(+) and CD4(+) T cell responses directly ex vivo at 4 to 8 years after exposure, demonstrating the longevity of T cell memory in humans. Second, unlike in murine models of LCMV infection, we found that the breadths of memory CD8(+) and CD4(+) T cell responses were not significantly different from one another. Third, it seemed that the overall CD8(+) T cell response was augmented with increasing severity of disease, while the LCMV-specific CD4(+) T cell response magnitude was highly variable between the three different donors. Next, we found that LCMV-specific CD8(+) T cells in the three donors analyzed seemed to undergo an effector memory differentiation program distinct from that of CD4(+) T cells. Finally, the levels of expression of memory, costimulatory, and inhibitory receptors on CD8(+) and CD4(+) T cell subsets, in some instances, correlated with disease outcome. These data demonstrate for the first time LCMV-specific CD8(+) and CD4(+) T cells in infected humans and begin to provide new insights into memory T cell responses following an acute virus infection.
authors: Pfizer Inc., Vaccine Research West, 10777 Science Center Drive, San Diego, CA 92121, USA. maya.kotturi@pfizer.com
authors: Maya F
authors: MF
authors: Kotturi
authors: Justine A
authors: JA
authors: Swann
authors: Bjoern
authors: B
authors: Peters
authors: Cecilia Lindestam
authors: CL
authors: Arlehamn
authors: John
authors: J
authors: Sidney
authors: Ravi V
authors: RV
authors: Kolla
authors: Eddie A
authors: EA
authors: James
authors: Rama S
authors: RS
authors: Akondy
authors: Rafi
authors: R
authors: Ahmed
authors: William W
authors: WW
authors: Kwok
authors: Michael J
authors: MJ
authors: Buchmeier
authors: Alessandro
authors: A
authors: Sette
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006805:Human Experimentation; D006801:Humans; D007156:Immunologic Memory; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008297:Male; D016602:Needlestick Injuries / Q000150:complications; D016273:Occupational Exposure / Q000009:adverse effects; D013997:Time Factors