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Abstract
"LONG-TERM MEMORY" AND "EFFECTOR MEMORY" CD4 PHENOTYPE BASED ON EXPRESSION OF CD62L AND CD45-ISOFORMS PREDICTS PATTERNS OF CELL DIVISION AND DIFFERENTIATION
HENGEL R, PAVLICK M, LEMPICKI R, METCALF J, LANE H
Background: Expression of the ligand (CD62L) that facilitates lymph-node entry through high endothelial venule can be used to characterize subsets of CD4 and CD8 T cells. The subset includes both “naïve” and “memory” cells, as defined by other markers, such as the CD45 isoforms RA and RO. Within the CD62L+ subset are the CD4 cells that proliferate in response to antigen and increase immediately after HAART. The purpose of the present study was to better characterize these cells.
Methods: PBMC from 13 donors (HIV-) were isolated then separated into CD4+ (or CD4+CD45RA-) subsets then CD62L+ and CD62L- subsets by magnetic beads. DNA was isolated and analyzed for telomer restriction fragment length (TRF, n=5). RNA was analyzed for differences in mRNA expression by DNA microarray (Affymetrix Inc., n=8).
Results: TRF length was lower in the CD62L- subset (6765 vs. 7874 bp, p=0.026). Compared to CD62L+, CD62L- cells had increased gene expresion for these protein groups: anti-microbial (e.g., cationic protein 37, defensins alpha 3 and 5), chemotaxis (CCR6, CCR9L) and differentiation (neuregulin 2, MIC1). Compared to CD62L-, CD62L+ cells had increases in these groups: neg regulation of transcription/division (DR1, MYC), telomer/DNA maint/repair (MRE11B, POLB), anti-differentiation (ICT1), endocytosis (AP2B1), kinases (SYK) and GTP/ATP assoc ( RANGAP1).
Conclusions: CD62L expression on “memory” CD4 cells characterizes a subset of cells that has undergone less cell division and less differentiation than cells without this marker. CD62L+ cells express genes associated with quiescence, energy storage, and surveillance while CD62L- cells express genes associated with anti-microbial function, chemotaxis and differentiation. These data suggest dramatic differences in the function and role of CD4 subsets based on expression of CD62L and justify its use, along with other markers such as CD45 isoforms, to characterize cells as “long-term (or central) ” or “effector memory” cells.
The 1st. IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
82
Suggested Citation
"HENGELR, et al.
"LONG-TERM MEMORY" AND "EFFECTOR MEMORY" CD4 PHENOTYPE BASED ON EXPRESSION OF CD62L AND CD45-ISOFORMS PREDICTS PATTERNS OF CELL DIVISION AND DIFFERENTIATION.
Oral Presentation:
The 1st. IAS Conference on HIV Pathogenesis and Treatment
:
Abstract no.
82"
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