Segregation of R5 and X4 HIV-1 variants to memory T cell subsets differentially expressing CD62L in ex vivo infected human lymphoid tissue.
OBJECTIVE
The mechanisms of HIV-triggered immunodeficiency were examined by determining the segregation of R5 and X4 HIV-1 variants into memory T cell subsets expressing differentially a homing receptor, CD62L-selectin, in human lymphoid tissue.


METHODS
Subpopulations of CD3 and intracellular p24 gag-positive cells in human lymphoid tissue infected ex vivo with X4 HIV-1 variant NL4-3 and R5 HIV-1 variant AD8 were analysed for expression of the T cell memory markers CD45RO and CD45RA, the T cell homing receptor for lymphoid tissue CD62L, and the HIV-1 coreceptors CCR5 and CXCR4.


RESULTS
Memory CD4 T cells were the predominant targets for productive infection of lymphoid tissue ex vivo with both R5 and X4 HIV-1. R5 HIV-1 predominantly infected CD62L-negative memory T cells, which selectively express CCR5. In contrast, X4 HIV-1 variants predominantly infected CD62L+ memory T cells, although CXCR4 coreceptor was equally expressed by memory T cells of both CD62L-positive and CD62L-negative subsets. A high proportion of X4 HIV-1, but not of R5 HIV-1, productively infected T cells, displayed a CD45RA+CD45RO+ phenotype.


CONCLUSIONS
The selective expression of the CCR5 coreceptor by CD62L-negative terminally differentiated memory T cells correlates with the preferential productive infection of these cells with the R5 HIV-1 variant. The predominance of X4 HIV-1 variants in less-differentiated memory T cells may be related to their recent activation state, as suggested by the coexpression of both CD45RA and CD45RO molecules on their surface. Differential homing of CD62L-positive and CD62L-negative cells suggests different routes of dissemination of X4 and R5 viruses.
Gondois-Rey
Françoise
F
INSERM U372, Unité de Pathogénie des Infections à Lentivirus, Marseille, France.
Grivel
Jean-Charles
JC
Biancotto
Angelique
A
Pion
Marjorie
M
Vigne
Robert
R
Margolis
Leonid B
LB
Hirsch
Ivan
I
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D005434:Flow Cytometry; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007156:Immunologic Memory; D019041:L-Selectin / Q000032:analysis / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000032:analysis; D008221:Lymphoid Tissue / Q000276:immunology* / Q000821:virology*; D019713:Receptors, CCR5 / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000821:virology*
D019713:Receptors, CCR5; D019041:L-Selectin; D017493:Leukocyte Common Antigens