Peripheral expansion of pre-existing mature T cells is an important means of CD4+ T-cell regeneration HIV-infected adults

Robert E. Walker, Charles S. Carter, Linda Muul, Ven Natarajan, Betsey R. Herpin, Susan F. Leitman, Harvey G. Klein, Craig A. Mullen, Julia A. Metcalf, Michael Baseler, Judith Falloon, Richard T. Davey, Joseph A. Kovacs, Michael A. Polis, Henry Masur, R. Michael Blaese, H. Clifford Lane

Research output: Contribution to journalArticle

Abstract

The CD4+ T-cell pool in HIV-infected patients is in a constant state of flux as CD4+ T cells are infected and destroyed by HIV and new cells take their place. To study T-cell survival, we adoptively transferred peripheral blood lymphocytes transduced with the neomycin phosphotransferase gene between syngeneic twin pairs discordant for HIV infection. A stable fraction of marked CD4+ T cells persisted in the circulation for four to eighteen weeks after transfer in all patients. After this time there was a precipitous decline in marked cells in three of the patients. At approximately six months, marked cells were in lymphoid tissues in proportions comparable to those found in peripheral blood. In two patients, the proportion of total signal for the transgene (found by PCR analysis) in the CD4/CD45RA+ T-cell population relative to the CD4/CD45RO+ population increased in the weeks after cell infusion. These findings indicate that genetically-marked CD4+ T cells persist in vivo for weeks to months and that the CD4+ T-cell pool in adults is maintained mostly by the division of mature T cells rather than by differentiation of prethymic stem cells. Thus, after elements of the T-cell repertoire are lost through HIV infection, they may be difficult to replace.

Original languageEnglish (US)
Pages (from-to)852-856
Number of pages5
JournalNature Medicine
Volume4
Issue number7
DOIs
StatePublished - Jul 1998
Externally publishedYes

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T-cells
Regeneration
HIV
T-Lymphocytes
HIV Infections
Blood
Kanamycin Kinase
Lymphocytes
Lymphoid Tissue
Stem cells
Transgenes
Population
Cell Differentiation
Cell Survival
Stem Cells
Genes
Tissue
Fluxes
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Walker, R. E., Carter, C. S., Muul, L., Natarajan, V., Herpin, B. R., Leitman, S. F., ... Lane, H. C. (1998). Peripheral expansion of pre-existing mature T cells is an important means of CD4+ T-cell regeneration HIV-infected adults. Nature Medicine, 4(7), 852-856. https://doi.org/10.1038/nm0798-852

Peripheral expansion of pre-existing mature T cells is an important means of CD4+ T-cell regeneration HIV-infected adults. / Walker, Robert E.; Carter, Charles S.; Muul, Linda; Natarajan, Ven; Herpin, Betsey R.; Leitman, Susan F.; Klein, Harvey G.; Mullen, Craig A.; Metcalf, Julia A.; Baseler, Michael; Falloon, Judith; Davey, Richard T.; Kovacs, Joseph A.; Polis, Michael A.; Masur, Henry; Blaese, R. Michael; Lane, H. Clifford.

In: Nature Medicine, Vol. 4, No. 7, 07.1998, p. 852-856.

Research output: Contribution to journalArticle

Walker, RE, Carter, CS, Muul, L, Natarajan, V, Herpin, BR, Leitman, SF, Klein, HG, Mullen, CA, Metcalf, JA, Baseler, M, Falloon, J, Davey, RT, Kovacs, JA, Polis, MA, Masur, H, Blaese, RM & Lane, HC 1998, 'Peripheral expansion of pre-existing mature T cells is an important means of CD4+ T-cell regeneration HIV-infected adults', Nature Medicine, vol. 4, no. 7, pp. 852-856. https://doi.org/10.1038/nm0798-852
Walker, Robert E. ; Carter, Charles S. ; Muul, Linda ; Natarajan, Ven ; Herpin, Betsey R. ; Leitman, Susan F. ; Klein, Harvey G. ; Mullen, Craig A. ; Metcalf, Julia A. ; Baseler, Michael ; Falloon, Judith ; Davey, Richard T. ; Kovacs, Joseph A. ; Polis, Michael A. ; Masur, Henry ; Blaese, R. Michael ; Lane, H. Clifford. / Peripheral expansion of pre-existing mature T cells is an important means of CD4+ T-cell regeneration HIV-infected adults. In: Nature Medicine. 1998 ; Vol. 4, No. 7. pp. 852-856.
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