Development and homeostasis of T cell memory in rhesus macaque

C. J. Pitcher, S. I. Hagen, J. M. Walker, R. Lum, B. L. Mitchell, V. C. Maino, Michael Axthelm, Louis Picker

Research output: Contribution to journalArticle

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Abstract

The rhesus macaque (RM) is a critical animal model for studies of viral pathogenesis and immunity, yet fundamental aspects of their cellular immune response remain poorly defined. One such deficiency is the lack of validated phenotypic signatures for their naive and memory T cell subsets, and the resultant unavailability of accurate information on their memory T cell development, homeostasis, and function. In this study, we report a phenotypic paradigm allowing definitive characterization of these subsets and their comprehensive functional analysis. Naive T cells are optimally delineated by their homogeneous CD95lowCD28highβ7 integrinint (CD4+) or CD95lowCD28intCD11alow (CD8+) phenotypes. This subset 1) was present in blood and secondary lymph tissues, but not effector sites; 2) vastly predominated in the fetal/neonatal immune system, but rapidly diminished with postnatal age; 3) lacked IFN-γ production capability, and specific responses to RM CMV; and 4) demonstrated low in vivo proliferative activity. CD4+ and CD8+ memory subsets were CD95high, but otherwise phenotypically heterogeneous and included all IFN-γ production, RM CMV-specific responses, effector site T cells, and demonstrated high in vivo proliferative activity (∼ 10 times the naive subset). These analyses also revealed the RM "effector memory" subset within the overall memory population. This population, best defined by lack of CD28 expression, contained the majority of RM CMV-specific cells, was highly enriched in extralymphoid effector sites, and comprised an increasing proportion of total memory cells with age. The effector memory subset demonstrated similar in vivo proliferative activity and survival as CD28+ "central memory" T cells, consistent with independent homeostatic regulation.

Original languageEnglish (US)
Pages (from-to)29-43
Number of pages15
JournalJournal of Immunology
Volume168
Issue number1
StatePublished - Jan 1 2002

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Macaca mulatta
Homeostasis
T-Lymphocytes
T-Lymphocyte Subsets
Lymph
Cellular Immunity
Population
Immune System
Immunity
Animal Models
Phenotype

ASJC Scopus subject areas

  • Immunology

Cite this

Pitcher, C. J., Hagen, S. I., Walker, J. M., Lum, R., Mitchell, B. L., Maino, V. C., ... Picker, L. (2002). Development and homeostasis of T cell memory in rhesus macaque. Journal of Immunology, 168(1), 29-43.

Development and homeostasis of T cell memory in rhesus macaque. / Pitcher, C. J.; Hagen, S. I.; Walker, J. M.; Lum, R.; Mitchell, B. L.; Maino, V. C.; Axthelm, Michael; Picker, Louis.

In: Journal of Immunology, Vol. 168, No. 1, 01.01.2002, p. 29-43.

Research output: Contribution to journalArticle

Pitcher, CJ, Hagen, SI, Walker, JM, Lum, R, Mitchell, BL, Maino, VC, Axthelm, M & Picker, L 2002, 'Development and homeostasis of T cell memory in rhesus macaque', Journal of Immunology, vol. 168, no. 1, pp. 29-43.
Pitcher CJ, Hagen SI, Walker JM, Lum R, Mitchell BL, Maino VC et al. Development and homeostasis of T cell memory in rhesus macaque. Journal of Immunology. 2002 Jan 1;168(1):29-43.
Pitcher, C. J. ; Hagen, S. I. ; Walker, J. M. ; Lum, R. ; Mitchell, B. L. ; Maino, V. C. ; Axthelm, Michael ; Picker, Louis. / Development and homeostasis of T cell memory in rhesus macaque. In: Journal of Immunology. 2002 ; Vol. 168, No. 1. pp. 29-43.
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